Vitamin D analogues

ABSTRACT

The invention concerns novel bi-aromatic compounds having the formula:                    
     which are analogs of vitamin D, the process of preparing them, as well as their use in pharmaceutical compositions in human or veterinary medicine, particularly in dermatology, cancer treatment, treatment of auto-immune diseases, and in organ or tissue transplants. Cosmetic compositions and methods of use are also included.

The invention relates, as new and useful industrial products, tobiaromatic compounds which are analogues of vitamin D. It also relatesto the process for their preparation and their use in pharmaceuticalcompositions intended for use in human or veterinary medicine, oralternatively in cosmetic compositions.

The compounds according to the invention have a marked activity in thefields of cell differentiation and proliferation and find applicationsmore particularly in the topical and systemic treatment ofdermatological conditions (and the like) linked to a keratinizationdisorder, of conditions with an inflammatory and/or immunoallergiccomponents and of hyperproliferation of tissues of ectodermal origin(skin, epithelium and the like), whether benign or malignant. Thesecompounds may, in addition, be used to combat skin ageing, whetherphotoinduced or chronologic, and to treat cicatrization disorders.

It is also possible to use the compounds according to the invention incosmetic compositions for body and hair hygiene.

Vitamin D is an essential vitamin for the prevention and treatment ofdefects in the mineralization of cartilage (rickets), and of bone(osteomalacia), and even of certain forms of osteoporosis in the elderlysubject. However, it is now accepted that these functions extend wellbeyond the regulation of bone metabolism and of calcium homeostasis.Among these, there may be mentioned its actions on cell proliferationand differentiation and the control of the immune defences. Theirdiscovery has opened the way for new therapeutic approaches indermatology, cancerology as well as in the field of autoimmune diseasesand that of organ and tissue transplants.

An effective therapeutic application has for long been hampered by thetoxicity of this vitamin (hypercalcaemia which is sometimes fatal).Currently, structural analogues of vitamin D are synthesized, some ofwhich conserve only the differentiating properties and have no action oncalcium metabolism.

One of the aims of the present invention is to provide new compoundswhich are structural analogues of vitamin D, which show a selectiveactivity on cell proliferation and differentiation without exhibiting ahypercalcaemic character.

Another aim of the present invention is to provide new compounds whichare analogues of vitamin D, which are easier to synthesize and thereforemore economical compared to what was previously known.

Thus, the present invention relates to compounds which may berepresented by the following general formula (I):

in which:

R₁ represents a hydrogen atom, a methyl radical or a radical—(CH₂)_(n)—OR₇,

R₂ represents a radical —(CH₂)_(n)—OR₈,

n, R₇ and R₈ having the meanings given below,

X—Y represents a bond chosen from the bonds of the following formulae(a) to (d) which may be read from the left to the right or conversely:

R₉ and W having the meanings given below,

R₃ represents the chain in vitamin D₂ or in vitamin D₃,

the dotted lines represent the bond linking the chain to the benzenering represented in Figure. (I),

or R₃ represents a chain having from 4 to 8 carbon atoms which issubstituted with one or more hydroxyl groups, it being possible for thehydroxyl groups to be protected in the form of acetoxy, methoxy orethoxy, trimethylsilyloxy, tert-butyldimethylsilyloxy,tetrahydropyranyloxy and optionally in addition:

which is substituted with one or more lower alkyl groups or cycloalkylgroups and/or

which is substituted with one or more halogen atoms and/or

which is substituted with one or more CF₃ groups and/or

in which one or more carbon atoms of the chain are replaced by one ormore oxygen, sulphur or nitrogen atoms, it being possible for thenitrogen atoms to be optionally substituted with lower alkyl radicalsand/or

in which one or more single bonds of the chain are replaced by one ormore double and/or triple bonds,

R₃ being positioned on the benzene ring at the para or meta positionwith respect to the X—Y bond,

R₄, R₅ and R₆, which are identical or different, represent a hydrogenatom, a lower alkyl radical, a halogen atom, a radical —OR₁₀, apolyether radical,

R₁₀ having the meaning given below,

n being 0, 1 or 2,

R₇ and R₈, which are identical or different, represent a hydrogen atom,an acetyl radical, a trimethylsilyl radical, a tert-butyldimethylsilylradical, a tetrahydropyranyl radical,

R₉ represents a hydrogen atom or a lower alkyl radical,

W represents an oxygen atom, a sulphur atom, a radical —CH₂— or aradical —NH— which may be optionally substituted with a lower alkylradical,

R₁₀ represents a hydrogen atom or a lower alkyl radical.

The invention also relates to the optical and geometric isomers of thesaid compounds of formula (I) as well as their salts in the case whereX—Y represent a bond of formula (a) and W represents a radical —NH—optionally substituted with a lower alkyl radical.

When the compounds according to the invention are provided in the formof salts, by addition of an acid, these are pharmaceutically orcosmetically acceptable salts obtained by addition of an inorganic ororganic acid, in particular hydrochloric, sulphuric, acetic, fumaric,hemisuccinic, maleic and mandelic acid.

According to the present invention, lower alkyl radical is understood tomean a linear or branched radical having from 1 to 6 carbon atoms, andpreferably the methyl, ethyl, isopropyl, tert-butyl and hexyl radicals.

Cycloalkyl radical is understood to mean a cyclic or polycyclic alkaneradical containing from 3 to 10 carbon atoms. Preferably, the cycloalkylradical is chosen from an adamantyl radical or a 1-methylcyclohexylradical.

Halogen atom is understood to mean preferably a fluorine, chlorine andbromine atom.

Polyether radical is understood to mean a radical having from 2 to 5carbon atoms which is interrupted by at least two oxygen atoms such asthe methoxymethoxy, methoxyethoxy and methoxyethoxymethoxy radicals.

Among the compounds of formula (I) which fall within the scope of thepresent invention, the following may be mentioned in particular:

3-Hydroxymethyl-5-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol,

3-Hydroxymethyl-5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol,

3-[3-(5-Hydroxy-1,5-dimethylhexyl)phenoxymethyl]-5-hydroxymethylphenol,

6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol,

6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methylhexan-2-ol,

6-[3-(3,4-Bis-hydroxymethylphenoxymethyl)phenyl]-2-methylheptan-2-ol,

7-[3-(3,4-Bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloctan-3-ol,

5-{2-[4-(5-Hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[4-(5-Hydroxy-5-methylhexyl)phenyl]ethyl}benzene-1,3-diol,

5-{2-[4-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[4-(6-Hydroxy-6-methylheptyl)phenyl]ethyl}benzene-1,3-diol,

5-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]ethyl}benzene-1,3-diol,

2-Hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol,

2-Hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol,

2-Hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol,

2-Hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol,

2-Hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylheptyl)phenyl]ethyl}phenol,

2-Hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]ethyl}phenol,

2-Hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol,

2-Hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol,

2-Hydroxymethyl-5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol,

6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methylheptan-2-ol,

4-[3-(5-Hydroxy-1,5-dimethylhexyl)phenoxymethyl]-2-hydroxymethylphenol,

6-{3-[2-(3,4-Bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol,

7-{4-[2-(3,4-Bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol,

6-{4-[2-(3,4-Bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol,

5-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]-1-methylvinyl}benzene-1,3-diol,

5-{2-[3-(5-Hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol,

5-[3-(6-Hydroxy-6-methylheptyl)phenoxymethyl]benzene-1,3-diol,

5-{2-[3-(7-Hydroxy-7-methyloct-1-enyl)phenyl]vinyl}-benzene-1,3-diol,

5-{2-[3-(7-Hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol,

4-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,2-diol,

3-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}phenol,

6-{3-[2-(3,5-Bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol,

3-{2-[3-(7-Hydroxy-7-methyloctyl)phenyl]vinyl}phenol,

7-{3-[2-(3,5-Bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol,

7-{3-[2-(3,4-Bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol,7-{3-[2-(4-Hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol,

4-{2-[3-(7-Hydroxy-7-methyloct-1-enyl)phenyl]vinyl}benzene-1,2-diol,

7-[3-(3,4-Bis-hydroxymethylphenylethynyl)phenyl]-2-methylheptan-2-ol,

5-{2-[3-(6-Hydroxy-6-methylhept-1-enyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(7-Ethyl-7-hydroxynon-1-enyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(7-Hydroxy-1-methoxy-1,7-dimethyloctyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(6-Hydroxy-1-methoxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(5-Hydroxypentyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(5-Hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(6-Hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol,

5-{2-[3-(5-Hydroxy-6-methylhept-1-enyl)phenyl]vinyl}-benzene-1,3-diol,

5-{2-[3-(6-Hydroxy-7-methyloct-1-enyl)phenyl]vinyl}-benzene-1,3-diol,

5-{2-[3-(1,6-Dihydroxy-1,6-dimethylheptyl)phenyl]-vinyl}benzene-1,3-diol,

5-{2-[3-(6-Hydroxy-1,6-dimethylhept-1-enyl)phenyl]-vinyl}benzene-1,3-diol,

6-{[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-methylamino}-2-methylhexan-2-ol,

5-{[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-methylamino}-2-methylpentan-2-ol,

6-{[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-methylamino}-3-ethylhexan-3-ol,

7-{[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-methylamino}-3-ethylheptan-3-ol,

5-{[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-ethylamino}-2-methylpentan-2-ol,

6-{[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-benzylamino}-3-ethylhexan-3-ol,

7-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylocta-4,6-dien-3-ol,

6-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-2-methylhepta-3,5-dien-2-ol,

7-{3-[2-(3,4-Bis-hydroxymethylphenyl)vinyl]phenyl}-3-ethylocta-4,6-dien-3-ol,

6-{3-[2-(3,4-Bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhepta-3,5-dien-2-ol,

7-[3-(3,4-Bis-hydroxymethylphenylethynyl)phenyl]-3-ethylocta-4,6-dien-3-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol,

(4E,6E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol,

(4E,6Z)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)pheny]-3-ethylocta-4,6-dien-3-ol,

7-[4-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol,

(4E,6E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol,

(4E,6Z)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol,

(E)-6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methylhept-3-en-2-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-4-en-3-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol,

(Z)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol,

(E)-8-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol,

(Z)-8-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol,

(E)-9-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol,

(Z)-9-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol,

8-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methyl-2-nonanol,

9-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldecan-3-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-4-yn-3-ol,

(3E,5E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2,7-dimethylocta-3,5-dien-2-ol,

(4E,6E)-7-[3-(3,4-Bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyl-octa-4,6-dien-3-ol,

(3E,5E)-6-[3-(3,4-Bis-hydroxymethylphenoxymethyl)phenyl]-2-methyl-hepta-3,5-dien-2-ol,

(Z)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-6-en-3-ol,

(Z)-6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-2-ol,

(Z)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-6-en-3-ol,

(Z)-6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-5-en-2-ol,

(Z)-8-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol,

(E)-8-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-non-7-en-3-ol,

8-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnonan-3-ol,

7-[5-(3,4-Bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol,

7-[5-(3,4-Bis-hydroxymethylbenzyloxy)-2-methylphenyl]-3-ethylnona-4,6-dien-3-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)-5-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)-4-methylphenyl]-3-ethylnona-4,6-dien-3-ol,

1-[3-(3,4)-Bis-hydroxymethylbenzyloxy)phenyl]ethanoneO-(2-hydroxy-2-methylpropyl)oxime,

1-{1-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-propoxy}-3-ethylpentan-3-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylnon-6-en-3-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylbenzylsulfanyl)phenyl]-3-ethyloct-6-en-3-ol,

(E)-7-{3-[(3,4-Bis-hydroxymethylbenzyl)methylamino]-phenyl}-3-ethyloct-6-en-3-ol,

(E)-6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-6-methylhept-4-en-3-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctan-3-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3,7-diethylnonan-3-ol,

(E)-6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-1,1,1-trifluoro-2-trifluoromethyl-oct-5-en-2-ol,

2-{4-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]hexyl}-1,1,1,3,3,3-hexafluoropropan-2-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoronon-6-en-3-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyloctan-3-ol,

(E)-6-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-3-ol,

(E)-4-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-1-cyclopropylhex-3-en-1-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnon-6-en-3-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methyldec-6-en-3-ol,

(4E,6E)-7-[3-(3,4-Bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylnona-4,6-dien-3-ol,

(4E,6E)-7-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]-phenyl}-3-ethylnona-4,6-dien-3-ol,

(E)-7-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylnon-6-en-3-ol,

(E)-3-Ethyl-7-[3-(3-hydroxymethylphenoxymethyl)phenyl]non-6-en-3-ol,

(E)-3-Ethyl-7-[3-(4-hydroxymethylphenoxymethyl)phenyl]-non-6-en-3-ol,

(E)-3-Ethyl-7-[(E)-3-(3-hydroxymethyl-4-methylphenoxymethyl)phenyl]non-6-en-3-ol,

(E)-3-Ethyl-7-[(E)-3-(4-hydroxymethyl-3-methyl-phenoxymethyl)phenyl]non-6-en-3-ol,

2-{4-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-4-methylpentyl}-1,1,1,3,3,3-hexafluoropropan-2-ol,

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyl-octan-3-ol,

7-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonan-3-ol

7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctane-3,4-diol

7-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonane-3,4-diol

7-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-7-methyloctane-3,4-diol

(E)-4-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-1-cyclopropylhex-3-en-1-ol

(4E,6E)-7-{3-[2-(3,4-Bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-4-methylnona-4,6-dien-3-ol

(4E,6E)-7-[3-(3,4-Bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnona-4,6-dien-3-ol

(E)-3-Ethyl-7-[3-(4-hydroxymethyl-3-methylphenoxymethyl)phenyl]non-6-en-3-ol,

(E)-3-Ethyl-7-[3-(3-hydroxymethyl-4-methylphenoxymethyl)phenyl]non-6-en-3-ol,

(E)-7-[3-(3,4-Bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloct-6-en-3-ol,

(E)-3-Ethyl-7-[3-(3-hydroxymethylphenoxymethyl)phenyl]-non-6-en-3-ol,

(E)-3-Ethyl-7-[3-(4-hydroxymethylphenoxymethyl)phenyl]-non-6-en-3-ol.

According to the present invention, the compounds of formula (I) whichare more particularly preferred are those for which at least one, andpreferably all the conditions below are observed:

R₁ represents the radical —(CH₂)_(n)OH,

R₂ represents the radical —(CH₂)_(n)OH,

X—Y represents a bond of formula (a) or (c),

R₃ represents a chain of 4 to 8 carbon atoms which is substituted withat least one hydroxyl radical and/or one lower alkyl radical.

The subject of the present invention is also the processes for thepreparation of the compounds of formula (I).

FIGS. 1 to 4 represent the reaction schemes which may be used for thepreparation of the compounds according to the invention.

Thus, the compounds of formula I(a) may be obtained (FIG. 1) by reactinga halogenated, preferably brominated, compound (1) with a phenol (W═OH),thiophenol (W═SH) or aniline (W═NH—COO-tert-butyl) derivative (3) in thepresence of a base such as K₂CO₃ in a solvent such as acetone or methylethyl ketone.

The compounds of formula I(a) may also be obtained (FIG. 1) by reactinga halogenated, preferably brominated, compound (1) with a sodium orpotassium salt of a phenol (W═OH), thiophenol (W═SH) or aniline(W═NH—COO-tert-butyl) derivative (3) in a solvent such asdimethylformamide (DMF).

The compounds of formula I(c) may be obtained (FIG. 1) by reacting abenzoic derivative (2) with a phenol (W═OH), thiophenol (W═SH) oraniline (W═NH₂) derivative (3) in the presence of carbonyldiimidazole orof dicyclohexylcarbodiimide in a solvent such as dichloromethane ortetrahydrofuran (THF).

The compounds of formula I(c) may also be obtained (FIG. 1) by reactinga benzoyl chloride (obtained by reacting a benzoic derivative (2) withthionyl chloride or oxalyl chloride) with a phenol (W═OH), thiophenol(W═SH) or aniline (W═NH₂) derivative (3) in the presence of a base suchas triethylamine in a solvent such as dichloromethane or tetrahydrofuran(THF).

The compounds of formula I(b) may be obtained (FIG. 2) by aHorner-Emmons-type reaction between the phosphonate derivative (4)(obtained from the corresponding benzyl bromide by an Arbuzov-typereaction) and benzaldehyde (5).

The compounds of formula I(a) may be obtained from compounds I(b) byhydrogenation in the presence of palladium on carbon.

The compounds of formula I(b) may also be obtained (FIG. 3) by aHeck-type reaction between an ethylenic derivative (7) (obtained byreacting benzaldehyde (5) with methyl triphenyl phosphine bromide) andthe triflate derivative (9) in the presence of a transition metalcatalyst such as Pd(Cl)₂(PPh₃)₂ in a solvent such as triethylamine.

The compounds of formula I(d) may be obtained (FIG. 3) by the reactionbetween an acetylenic derivative (8) (obtained from benzaldehyde (5) bya Corey-Fuchs-type reaction) and a triflate derivative (9) in thepresence of a transition metal catalyst Pd(Cl)₂(PPh₃)₂ and of CuI in asolvent such as triethylamine.

The chain R₃ may be introduced using, for example, the methods describedin Medicinal Research Reviews, Vol 7, No. 2, 147-171 (1987) T. KAMETANIand H. FURUYAMA, Chem. Rev. Vol 78, No. 3, 199-241 (1978) D. M. PIATAKand J. WICHA, or in Chem. Rev. Vol 95, No. 6, 1877-1952 (1995) G. ZHUand W. H. OKAMURA.

Thus, by way of examples, a few summarized methods are given in FIG. 4,in which (a) represents a reaction withMgBr—CH₂—(CH₂)_(n)—C(CH₃)₂—O-tetrahydropyran in a solvent such astetrahydrofuran, (b) represents a reaction in the presence ofpara-toluenesulphonic acid or sulphuric acid, (c) represents ahydrogenation reaction in the presence of palladium-on-carbon catalyst,(d) represents a reduction reaction with sodium borohydride in amethanol-tetrahydrofuran solvent, (e) represents a reaction withBr—CH₂(CH₂)_(n)—CH₂—COOR in the presence of potassium hydride in adimethylformamide solvent, (f) represents a reaction with MgXAlkyl, Xrepresenting a halogen atom, in a tetrahydrofuran solvent, (g)represents a reaction with NC—CH₂—P(O)(OC₂H₅)₂ in the presence of sodiumhydride in a tetrahydrofuran solvent, (h) represents a reaction withdiisobutylaluminium hydride in a tetrahydrofuran solvent, (i) representsa reaction with carbon tetrabromide in the presence oftriphenylphosphine in a mixture of tetrahydrofuran followed by areaction with n-butyllithium, (j) represents a reaction withn-butyllithium in tetrahydrofuran, (k) represents a reaction with thealkyl chloroformate Cl—COOR, (l) represents a reaction with MgXAlkyl, Xrepresenting a halogen atom, in a tetrahydrofuran solvent, (m)represents a reaction with n-butyllithium in tetrahydrofuran, (n)represents a reaction with CF₃—CO—CF₃, (o) represents a reaction withROOC—CH═CH—CH₂—P(O) (OC₂H₅)₂ in the presence of lithium iisopropylamidein tetrahydrofuran, (p) represents a reaction with MgXAlkyl, Xrepresenting a halogen atom, n a tetrahydrofuran solvent.

The compounds of general formula (I) exhibit biological propertiessimilar to those of vitamin D, in particular the vitamin D responseelement (VDRE) transactivating properties, such as an agonist orantagonist activity towards receptors for vitamin D or its derivatives.Vitamins D or their derivatives are understood to mean, for example, thederivatives of vitamin D₂ or D₃ and in particular 1,25-dihydroxy vitaminD₃ (calcitriol).

This agonist activity towards receptors for vitamin D or its derivativesmay be demonstrated “in vitro” by methods recognized in the field of thestudy of gene transcription (Hansen et al., The Society forInvestigative Dermatology, vol. 1, No. 1, April 1996).

By way of example, the VDR agonist activity may be tested on the HeLacell line, by cotransfecting a human VDR receptor expression vector andthe reporter plasmid p240Hase-CAT which contains the region—1399 to +76of the promoter of rat 24-hydroxylase, cloned upstream of the codingphase of the chloramphenicol acetyl transferase (CAT) gene. 18 hoursafter cotransfection, the test product is added to the medium. After 18hours of treatment, the assay of the CAT activity in the cell lysates iscarried out by an Elisa test. The results are expressed as percentage ofthe effect normally observed with 10⁻⁷ M calcitriol.

The agonist activity may also be characterized in this cotransfectionsystem by the determination of the dose necessary to reach 50% of themaximum activity of the product (AC50).

The biological properties which are similar to vitamin D may also bemeasured by the capacity of the product to inhibit the proliferation ofnormal human keratinocytes (NHK in culture). The product is added toNHKs cultured under conditions promoting the proliferative state. Theproduct is left in contact with the cells for 5 days. The number ofproliferative cells is measured by incorporation of bromodeoxyuridine(BRdU) into DNA.

The agonist activity towards the vitamin D receptors of the compounds ofthe invention may also be evaluated “in vivo” by induction of24-Hydroxylase in SKH mice (Voorhees et al. 1997.108: 513-518). The testprotocol used is described in Example 54 of the present application.

The subject of the present invention is also, as a medicament, thecompounds of formula (I) as described above.

The compounds according to the invention are particularly suitable inthe following fields of treatment:

1) For treating dermatological conditions linked to a keratinocyte orsebocyte differentiation or proliferation disorder, in particular fortreating acne vulgaris, comedo-type acne, polymorphic acne, acnerosacea, nodulocystic acne, acne conglobata, senile acne, secondary acnesuch as solar acne, acne medicamentosa or occupational acne.

2) For treating other types of keratinization disorders, in particularichthyosis, ichthyosiform states, Darier's disease, keratosis palmariset plantaris, leukoplasia, leukoplasiform states, cutaneous or mucosal(buccal) lichen.

3) For treating other dermatological conditions linked to akeratinization disorder with an inflammatory and/or immunoallergiccomponent, and in particular all the forms of psoriasis, whethercutaneous, mucosal or ungual, and even psoriatic rheumatism or cutaneousatopy, such as eczema or respiratory atopy or gingival hypertrophy; thecompounds may also be used in certain inflammatory conditions which donot exhibit keratinization disorders.

4) For treating any dermal or epidermal proliferations whether benign ormalignant, whether of viral origin or not, such as verruca vulgaris,verruca plana and epidermodysplasia verruciformis, oral or floridpapillomatoses and proliferations which may be induced by ultravioletradiation in particular in the case of baso- and spinocellularepithelioma.

5) For treating other dermatological disorders such as bullousdermatoses and collagen diseases.

6) For repairing or combating skin ageing, whether photoinduced orchronologic, or for reducing pigmentations and actinic keratoses, or anypathologies associated with chronologic or actinic ageing.

7) For preventing or treating cicatrization disorders or for preventingor repairing vibices.

8) For combating disorders of the sebaceous function, such ashyperseborrhoea of acne or simple seborrhoea or seborrhoeic eczema.

9) For treating certain ophthalmological disorders, in particularcorneopathies.

10) In the treatment or prevention of cancerous or precancerous statesof cancers exhibiting or capable of being induced so as to exhibitvitamin D receptors, such as, but without limitation, breast cancer,leukaemia, myelodysplasic syndromes and lymphomas, carcinomas of thecells of the Malpighian epithelium and gastrointestinal cancers,melanomas and osteosarcoma.

11) In the treatment of inflammatory conditions such as arthritis orrheumatoid arthritis.

12) In the treatment of any condition of viral origin at the cutaneouslevel or in general.

13) In the prevention or treatment of alopecia of various origins, inparticular alopecia due to chemotherapy or to radiation.

14) In the treatment of dermatological or general conditions with animmunological component.

15) In the treatment of immunological conditions such as autoimmunediseases (such as, but without limitation, type 1 diabetes mellitus,multiple sclerosis, lupus and lupus-type conditions, asthma,glomerulonephritis and the like), selective dysfunctions of the immunesystem (for example AIDS) and the prevention of immune rejection [suchas the rejection of grafts (for example the kidney, heart, bone marrow,liver, pancreatic islets or the whole pancreas, the skin and the like)or the prevention of graft-versus-host disease].

16) In the treatment of hormonal conditions given that the vitamin Danalogues can modulate hormonal secretion such as the increase in thesecretion of insulin or the selective suppression of the secretion ofthe parathyroid hormone (for example in chronic renal insufficiency andsecondary hyperparathyroidism).

17) In the treatment of conditions characterized by an abnormalmanagement of intracellular calcium.

18) In the treatment and/or prevention of vitamin D deficiencies and ofother conditions of the homeostasis of the minerals in the plasma andthe bones, such as rickets, osteomalacia, osteoporosis, in particular inthe case of menopausal women, renal osteodystrophy, parathyroid functiondisorders.

In the abovementioned therapeutic fields, the compounds according to theinvention may be advantageously used in combination with retinoids, withcorticosteroids or oestrogens, in combination with antioxidants, withα-hydroxy or α-keto acids or derivatives thereof, with potassium channelblockers, or alternatively in combination with other medicaments knownto interfere with the immune system (for example cyclosporin, FK 506,glucocorticoids, monoclonal antibodies, cytokines or growth factors andthe like).

Retinoids are understood to mean ligands for the RAR or RXR receptors,either natural or synthetic.

Anti-free radicals are understood to mean, for example, α-tocopherol,Super Oxide Dismutase, Ubiquinol or some metal chelators.

α-Hydroxy or α-keto acids or derivatives thereof are understood to mean,for example, lactic, malic, citric, glycolic, mandelic, tartaric,glyceric or ascorbic acids, or salicylic acid derivatives, as well astheir salts, amides or esters.

Potassium channel blockers are understood to mean, for example,Minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) and itsderivatives.

The subject of the present invention is also a pharmaceuticalcomposition comprising at least one compound of formula (I) as definedabove.

The subject of the present invention is therefore also such apharmaceutical composition intended in particular for the treatment ofthe abovementioned conditions.

The administration of the compounds according to the invention may becarried out by the enteral, parenteral, topical or ocular route.

By the enteral route, the pharmaceutical compositions may be provided inthe form of tablets, gelatin capsules, sugar-coated tablets, syrups,suspensions, solutions, powders, granules, emulsions, lipid or polymericmicrospheres or nanospheres or vesicles which allow a controlledrelease. By the parenteral route, the compositions may be provided inthe form of solutions or suspensions for infusion or for injection.

The compounds according to the invention are generally administered at adaily dose of about 0.001 μg/kg to 1000 μg/kg and preferably about 0.01μg/kg to 100 μg/kg as bodyweight, in 1 to 3 doses.

By the topical route, the pharmaceutical compositions based on compoundsaccording to the invention are intended for the treatment of the skinand the mucous membranes and are provided in the form of salves, creams,milks, ointments, powders, impregnated pads, solutions, gels, sprays,lotions or suspensions. They may also be provided in the form of lipidor polymeric microspheres or nanospheres or vesicles or of polymericpatches and hydrogels allowing a controlled release. These compositionsfor the topical route may be provided either in anhydrous form or in anaqueous form, depending on the clinical indication.

By the ocular route, they are mainly collyria

These compositions for the topical or ocular route contain at least onecompound of formula (I) as defined above at a concentration preferablyof between 0.0001 and 5% and preferably between 0.001 to 1% relative tothe total weight of the composition.

The compounds of formula (I) according to the invention also findapplication in the cosmetic field, in particular in body and hair careand in particular for the treatment of skins with a tendency towardsacne, for hair regrowth, against hair loss, for combating the greasyappearance of the skin or the hair, in protecting against the harmfuleffects of the sun and in the treatment of physiologically dry skins,for preventing and/or for combating photoinduced or chronologic ageing.

In the cosmetic field, the compounds according to the invention may beadvantageously used in combination with retinoids, with corticosteroids,in combination with anti-free radicals, with α-hydroxy or α-keto acidsor derivatives thereof, or alternatively with ion-channel blockers.

The various products taken in combination with the compounds of thepresent invention are as defined above.

The present invention therefore also relates to a cosmetic compositioncontaining, in a cosmetically acceptable carrier, at least one compoundof formula I as defined above. This cosmetic composition may be providedin particular in the form of a cream, a milk, a lotion, a gel, lipid orpolymeric microspheres or nanospheres or vesicles, a soap or a shampoo.

The concentration of compound of formula I in the cosmetic compositionsmay be between 0.001 and 3% by weight relative to the total weight ofthe composition.

The pharmaceutical and cosmetic compositions according to the inventionmay, in addition, contain inert or even pharmacodynamically orcosmetically active additives or combinations of these additives, and inparticular: wetting agents; depigmenting agents such as hydroquinone,azelaic acid, caffeic acid or kojic acid; emollients; moisturizingagents such as glycerol, PEG 400, thiamorpholinone, and its derivativesor urea; antiseborrhoeic or antiacne agents, such asS-carboxymethylcysteine, S-benzylcysteamine, their salts or theirderivatives, or benzoyl peroxide; antibiotics such as erythromycin andits esters, neomycin, clindamycin and its esters, tetracyclines;antifungal agents such as ketoconazole or4,5-polymethylene-3-isothiazolinones; agents promoting hair regrowth,such as Minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) and itsderivatives, Diazoxide (7-chloro 3-methyl-1,2,4-benzothiadiazine1,1-dioxide) and Phenytoin (5,4-diphenyl-2,4-imidazolidinedione);nonsteroidal anti-inflammatory agents; carotenoids and, in particular,β-carotene; antipsoriatic agents such as anthralin and its derivatives;and finally 5,8,11,14-eicosatetraynoic and 5,8,11-eicosatrynoic acids,their esters and amides.

The compositions according to the invention may also containtaste-enhancing agents, preservatives such as para-hydroxybenzoic acidesters, stabilizing agents, moisture-regulating agents, pH-regulatingagents, osmotic pressure-modifying agents, emulsifying agents, UV-A andUV-B screening agents, antioxidants such as α-tocopherol, butylatedhydroxyanisole or butylated hydroxytoluene.

Several examples of producing active compounds of formula (I) accordingto the invention, as well as various concrete formulations based on suchcompounds as well as an example of a test for evaluating the biologicalactivity of the compounds of formula (I) according to the invention willnow be given, by way of illustration and without any limitation.

EXAMPLE 13-Hydroxymethyl-5-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol

a) Methyl 5-Hydroxyisophthalate.

30 ml of concentrated sulphuric acid are added, dropwise, to a solutionof 54.6 g (0.3 mol) of 5-hydroxyisophthalic acid in 500 ml of methanol.The reaction medium is heated under reflux for 24 hours. Afterevaporation, the residue is taken up in ethyl acetate and extracted withwater. The organic phase is dried over anhydrous magnesium sulphate andthen concentrated. The residue is triturated in heptane.

White solid. m=59.8 g. Y=95%. m.p.=162-4° C. ¹H NMR (CDCl₃): 3.91 (6H,s) 7.71 (2H, d), 8.15-8.16 (1H, t).

b) 5-Hydroxyisophthalic Acid Monomethyl Ester.

119 g (2.8 mol) of lithium hydroxide monohydrate are added to a solutionof 59.7 g (0.28 mol) of methyl 5-hydroxyisophthalate in 500 ml of THF.The mixture is heated under reflux for 24 hours. At room temperature, itis gently poured into concentrated hydrochloric acid, extracted withethyl acetate and washed with water. After decantation, the organicphase is dried over magnesium sulphate and concentrated. The residue ispurified on a silica column (dichloromethane 93-heptane 7).

White crystals. m=40 g. Y=78%. m.p.=238-40° C. ¹H NMR (DMSO): 3.87 (3H,s), 7.54-7.58 (2H, m), 7.95-7.96 (1H, t).

c) Methyl 3-Hydroxy-5-hydroxymethylbenzoate.

375 ml of borane 1M/THF are added, dropwise, at 0° C., to a solution of37 g (0.19 mol) of 5-hydroxyisophthalic acid monomethyl ester in 200 mlof THF. At the end of the addition, the medium is heated at 40° C. for12 hours. 200 ml of a THF/water solution (1/1) are added very slowly.After having evaporated the THF, the remaining aqueous phase isextracted with dichloromethane and then potassium carbonate is added.After decantation, the organic phase is washed with water and then driedover magnesium sulphate and concentrated. The residue is filtered onsilica with ethyl acetate.

White crystals. m=27 g. Y=78%. ¹H NMR (CDCl₃): 3.87 (3H, s), 4.62-4.64(2H, d), 7.09 (1H, s), 7.39-7.41 (1H, t), 7.51 (1H, s), 8.96 (1H, s).

d) Methyl 3-Ethoxymethoxy-5-ethoxymethoxymethylbenzoate.

26 g (143 mmol) of methyl 3-hydroxy-5-hydroxymethylbenzoate in 200 ml ofdimethylformamide are added, dropwise, to a solution of 11 g (344 mmol)of sodium hydride (75%) in 100 ml of DMF. The medium is stirred for 1hour and then 29.1 ml (314 mmol) of methoxymethyl chloride are addedslowly. The stirring is continued overnight. The medium is then pouredinto ice-cold water and extracted with ethyl acetate. The organic phaseis dried over magnesium sulphate and then concentrated. The residue ispurified on a silica column (dichloromethane 90-heptane 10).

Yellow oil. m=26.5 g. Y=63%. ¹H NMR (CDCl₃): 1.19-1.26 (6H, m),3.61-3.77 (4H, m), 3.91 (3H, s), 4.61 (2H, s), 4.77 (2H, s), 5.26 (2H,s), 7.23 (1H, s), 7.61-7.62 (1H, c), 7.67 (1H, s).

e) (3-Ethoxymethoxy-5-ethoxymethoxymethylphenyl)methanol.

203 ml of diisobutylaluminium hydride 1M/toluene are added, at −78° C.,dropwise, to a solution of 20 g (68 mmol) of methyl3-ethoxymethoxy-5-ethoxymethoxymethylbenzoate in 150 ml of toluene. Thissolution is stirred for 2 hours at −78° C. A solution of 32 g of sodiumtartrate in 300 ml of water is then added. The white solid formed isfiltered and the filtrate is evaporated. The residue is taken up inethyl acetate and poured into ice. The organic phase is washed severaltimes with water and then dried over magnesium sulphate and thenconcentrated. The residue is purified on a silica column (ethyl acetate30-heptane 70).

Yellow oil. m=14.5 g. Y=79%. ¹H NMR (CDCl₃): 1.19-1.26 (6H, m),1.94-1.98 (1H, OH, t), 3.59-3.76 (4H, m), 4.56 (2H, s), 4.64-4.66 (2H,d), 4.75 (2H, s), 5.22 (2H, s), 6.96-6.99 (3H, m).

f) 3-Ethoxymethoxy-5-ethoxymethoxymethylbenzaldehyde.

4.9 ml of acetic acid are added, dropwise, at 10° C., to a solution of13.5 g (0.05 mol) of(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)methanol, 28.2 g (0.075mol) of pyridinium dichromate and 30 g of ground molecular sieve in 250ml of anhydrous dichloromethane. After stirring for 15 minutes at roomtemperature, 300 ml of ether are added. The precipitate formed isfiltered on silica, rinsed with ether and then the filtrate isevaporated. The residue is purified on a silica column (dichloromethane20-heptane 80).

Yellow oil. m=10 g. Y=75%. ¹H NMR (CDCl₃): 1.19-1.27 (6H, m), 3.62-3.78(4H, m), 4.65 (2H, s), 4.79 (2H, s), 5.28 (2H, s), 7.29 (1H, s), 7.47(1H, s), 7.52 (1H, s), 9.97 (1H, s).

g) 3-Bromo-[2-(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl.

290 mg (8.9 mmol) of sodium hydride 75% are added, in small quantities,to a solution of 2 g

(7.4 mmol) of 3-ethoxymethoxy-5-ethoxymethoxymethylbenzaldehyde and 2.7g (8.8 mmol) of ethyl (3-bromobenzyl)phosphonate in 60 ml of THF withone drop of 15-Crown-5. The mixture is stirred overnight at roomtemperature. It is then concentrated, taken up in ethyl ether and washedseveral times with water. After decantation, the organic phase is driedover magnesium sulphate and concentrated. The residue is purified on asilica column (ethyl acetate 10-heptane 90).

Yellow oil. m=2.8 g. Y=89%. ¹H NMR (CDCl₃): 1.18-1.28 (6H, m), 3.63-3.79(4H, m), 4.60 (2H, s), 4.79 (2H, s), 5.26 (2H, s), 6.96 (1H, s),7.03-7.04 (2H, d), 7.11-7.16 (1H, d, J=12.1 Hz), 7.22-7.25 (1H, d, J=7.8Hz), 7.36-7.42 (2H, m), 7.65-7.66 (1H, t).

h) Methyl5-{3-[2-(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl)pentanoate.

A solution of 1.4 g (5.7 mmol) of 9-borabicyclo[3.3.1]nonane in 15 ml ofTHF is added, dropwise, at 0° C., to 420 mg (3.7 mmol) of methylpent-4-enoate. It is stirred for 5 hours at room temperature. 1.25 g (3mmol) of3-bromo-[2-(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl in10 ml of dimethylformamide, 850 mg (6 mmol) of potassium carbonate and150 mg (0.18 mmol) of[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium are then added.The mixture is stirred at 50° C. overnight. Dichloromethane is added andthe organic phase is then washed several times with water. Afterdecantation, it is dried over magnesium sulphate and concentrated. Theresidue is purified on a silica column (ethyl acetate 8-heptane 92).

Yellow oil. m=830 mg. Y=61%. ¹H NMR (CDCl₃): 1.21-1.28 (6H, m), 1.69(4H, m), 2.35 (2H, m), 2.65 (2H, t), 3.67 (3H, s), 3.63-3.79 (4H, m),4.60 (2H, s), 4.79 (2H, s), 5.26 (2H, s), 7.07-7.16 (5H, m), 7.25-7.32(3H, m).

i)6-{3-[2-(3-Ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol.

3.6 ml (10.8 mmol) of methylmagnesium bromide 3M/ether are added,dropwise, to 820 mg (1.8 mmol) of methyl5-{3-[2-(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl}pentanoatein 20 ml of ethyl ether. The mixture is stirred for 1 hour at roomtemperature. A saturated aqueous ammonium chloride solution is then veryslowly added as well as ether. The organic phase is washed several timeswith water and, after decantation, it is dried over magnesium sulphateand concentrated. The residue is purified on a silica column (ethylacetate 25-heptane 75).

Yellow oil. m=600 mg. Y=73%. ¹H NMR (CDCl₃): 1.22 (6H, s), 1.18-1.25(6H, m), 1.50-1.60 (6H, m), 2.58-2.66 (2H, m), 3.57-3.86 (4H, m, 4.60(2H, s), 4.79 (2H, s), 5.27 (2H, s), 6.94 (1H, c), 7.08-7.17 (6H, m),7.33 (2H, c).

j) 3-Hydroxymethyl-5-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol.

A solution of 0.3 ml of concentrated sulphuric acid in 5 ml of methanolis added to 600 mg (1.3 mmol) of6-{3-[2-(3-ethoxymethoxy-5-ethoxymethoxyphenyl)vinyl]phenyl}2-methylhexan-2-olin 5 ml of methanol and 5 ml of THF. After 4 hours at room temperature,water and ethyl acetate are added. The organic phase is washed severaltimes with water and then dried over magnesium sulphate andconcentrated. The residue is purified on a silica column (ethyl acetate50-heptane 50).

White crystals m=300 mg. Y=67%. m.p.=108-10° C. ¹H NMR (CDCl₃): 1.20(6H, s), 1.38-1.54 (4H, m), 1.59-1.71 (2H, m), 2.61-2.67 (2H, t), 4.61(2H, s), 6.80 (1H, s), 6.90 (1H, s), 7.04-7.08 (4H, m), 7.21-7.29 (3H,m), 8.74 (1H, OH, s).

EXAMPLE 23-Hydroxymethyl-5-{2-[2-(6-hydroxy-6-methylphenyl)phenyl]vinyl}phenol

a) Methyl6-{3-[2-(3-ethoxymethoxy-5-ethoxymethoxymethyl)vinyl]phenyl}hexanoate.

In a manner similar to Example 1(h), by reacting 1.3 g (3 mmol) of3-bromo-[2-(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl in10 ml of dimethylformamide with the solution, at 0° C., of 1.4 g (5.7mmol) of 9-borabicyclo[3.3.1]nonane and 475 mg (3.7 mmol) of methylhex-5-enoate in 15 ml of THF, a yellow oil (m=1.08 g; Y=74%) isobtained, after purification on a silica column (ethyl acetate 8-heptane92).

¹H NMR (CDCl₃): 1.21-1.28 (6H, m), 1.64-1.67 (2H, m), 1.85 (4H, m),2.29-2.35 (2H, t), 2.60-2.66 (2H, t), 3.66 (3H, s), 3.63-3.79 (4H, m),4.60 (2H, s), 4.79 (2H, s), 5.26 (2H, s), 6.94 (1H, s), 7.08-7.16 (5H,m), 7.23-7.32 (3H, m).

b)7-{3-[2-(3-Ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 1(i), by reacting 3.8 ml (11.4 mmol) ofmethylmagnesium bromide 3M/ether with 1.08 g (2.3 mmol) of methyl6-{3-[2-(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl}hexanoatein 20 ml of ethyl ether, a yellow oil (m=480 mg; Y=44%) is obtainedafter purification on a silica column (ethyl acetate 30-heptane 70).

¹H NMR (CDCl₃): 1.21 (6H, s), 1.22-1.28 (6H, m), 1.40-1.66 (8H, m),2.60-2.66 (2H, t), 3.63-3.79 (4H, m), 4.60 (2H, s), 4.79 (2H, s), 5.26(2H, s), 6.93 (1H, s), 7.07-7.16 (5H, s), 7.29-7.32 (3H, m).

c)3-Hydroxymethyl-5-{2-[3-(6-hydroxy-6-methyl-heptyl)phenyl]vinyl}phenol.

In a manner similar to Example 1(j), by reacting 0.3 ml of concentratedsulphuric acid in 5 ml of methanol with 470 mg (1.0 mmol) of7-{3-[2-(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-olin 5 ml of methanol and 5 ml of THF, a colourless oil (m=109 mg; Y=31%)is obtained after purification on a silica column (ethyl acetate40-heptane 60).

¹H NMR (CDCl₃): 1.21 (6H, s), 1.39-1.66 (8H, m) 2.59-2.65 (2H, t), 4.66(2H, s), 6.76 (1H, s), 6.90 (1H, s), 7.03-7.09 (4H, m), 7.26-7.30 (3H,m).

EXAMPLE 33-[3-(5-Hydroxy-1,5-dimethylhexyl)phenoxymethyl]-5-hydroxymethylphenol

a) (3-Ethoxymethoxy-5-ethoxymethoxymethylphenyl)methanol.

135 mg (3.55 mmol) of sodium borohydride are added, in small quantities,to a solution of 1.9 g (7.1 mmol) of3-ethoxymethoxy-5-ethoxymethoxymethylbenzaldehyde in 30 ml of methanoland 20 ml of THF. After having been stirred for 15 minutes at roomtemperature, the medium is poured into water and extracted with ethylacetate. After decantation, the organic phase is dried over magnesiumsulphate and concentrated.

Yellow oil. m=1.9 g. Y=100%. ¹H NMR (CDCl₃): 1.19-1.26 (6H, m),3.61-3.77 (4H, m), 4.57 (2H, s), 4.66 (2H, s), 4.85 (2H, s), 5.23 (2H,s), 6.96-7.00 (3H, m).

b) 1-Bromomethyl-3-ethoxymethoxy-5-ethoxymethoxymethylbenzene.

At 0° C., 6.9 ml (15.4 mmol) of trioctylphosphine are added to asolution of 1.9 g (7 mmol) of(3-ethoxymethoxy-5-ethoxymethoxymethylphenyl)methanol and 5.1 g (15.4mmol) of carbon tetrabromide in 50 ml of ethyl ether. After 15 minutesat 0° C., ether is added and the medium is washed several times withwater. After decantation, the organic phase is dried over magnesiumsulphate and concentrated. The residue is purified on a silica column(AcOEt8-heptane 92).

Yellow oil. m=1.5 g. Y=64%. ¹H NMR (CDCl₃): 1.19-1.26 (6H, s), 3.61-3.77(4H, m), 4.45 (2H, s), 4.54-4.57 (2H, m), 4.76 (2H, s), 5.22 (2H, s),6.97-7.02 (3H, m).

c) 1-[3-(tert-Butyldimethylsilanyloxy)phenyl]-ethanone.

45.2 g (0.3 mol) of tert-butyldimethylsilane chloride in 250 ml ofdimethylformamide are added, dropwise, to a solution of 34 g (0.25 mol)of 3-hydroxyacetophenone in 200 ml of DMF with 38.2 ml (0.27 mol) oftriethylamine and 1.2 g (9.8 mmol) of dimethylaminopyridine. The mixtureis stirred for 2 hours 30 minutes at room temperature. It is then pouredinto ice-cold water and extracted with ether. The organic phase is driedover magnesium sulphate and concentrated. The residue is purified on asilica column (dichloromethane 40-heptane 60).

Orange-coloured oil. m=57 g. Y=91%. ¹H NMR (CDCl₃): 0.01 (6H, s), 0.79(9H, s), 2.38 (3H, s), 6.82-6.85 (1H, dd), 7.06-7.15 (1H, m), 7.20-7.22(1H, t), 7.33-7.36 (1H, d, J=7.6 Hz).

d) 3-[3-tert-Butyldimethylsilanyloxy)phenyl]but-2-enenitrile.

62 ml (0.38 mol) of diethylcyanomethylphosphonate in 200 ml of THF areadded, dropwise, at 0° C., to a solution of 12.2 g (0.38 mol) of sodiumhydride in 50 ml of THF. The mixture is stirred for 2 hours at roomtemperature. 57 g (0.23 mol) of1-[3-(tert-butyldimethylsilanyloxy)phenyl]ethanone in 200 ml of THF arethen added at 0C. The temperature is allowed to rise and the mixture isstirred for 4 hours. After evaporation of the THF, the product is takenup in ethyl ether. The ethereal phase is washed several times withwater. After decantation, the organic phase is dried over magnesiumsulphate and concentrated. The residue is purified on a silica column(heptane).

Yellow oil. m=58.3 g. Y=94%. ¹H NMR (CDCl₃): 0.01 (6H, s), 0.79 (9H, s),2.24 (3H, d, J=1 Hz), 5.38-5.39 (1H, d, J=1 Hz), 6.67-6.70 (2H, m),6.83-6.87 (1H, dd), 7.02-7.08 (1H, m).

e) 3-[3-(tert-Butyldimethylsilanyloxy)phenyl]but-2-enal.

In a manner similar to Example 1(e), by reacting 280 ml ofdiisobutylaluminium hydride 1M/toluene, at −78° C., with 58.2 g (0.21mol) of 3-[3-(tert-butyldimethylsilanyloxy)phenyl]but-2-enenitrile, anorange-coloured oil (m=28.5 g; Y=48%) is obtained after purification ona silica column (dichloromethane 50-heptane 50).

¹H NMR (CDCl₃): 0.01 (6H, s), 0.79 (9H, s), 2.34 (3H, d, J=1.1 Hz),6.14-6.18 (1H, d, J=6.7 Hz), 6.67-6.71 (1H, dd), 6.79-6.80 (1H, t),6.92-6.95 (1H, d), 7.03-7.10 (1H, m), 9.96-9.99 (1H, d, J=7.9 Hz).

f) Ethyl 5-[3-(tert-butyldimethylsilanyloxy)phenyl]-hexa-2,4-dienoate.

62 ml (154 mmol) of n-butyllithium 2.5 M/hexane are added, dropwise, at0° C., to 150 ml of THF and 150 ml of HMPA. Rapidly, at −30° C., 21.5 ml(154 mmol) of diisopropylamine are added, followed, at −60° C. anddropwise, by 28.5 ml (144 mmol) of triethylphosphonoacetate. The mixtureis stirred for 1 hour at −60° C. and then a solution of 28.4 g (103mmol) of 3-[3-(tert-butyldimethylsilanyloxy)phenyl]but-2-enal in 60 mlof THF is added dropwise. The temperature is allowed to rise to roomtemperature. The solvents are evaporated and the residue is taken up inethyl ether. The organic phase is extracted with a saturated aqueousammonium chloride solution and then washed several times with water.After decantation, it is dried over magnesium sulphate and concentrated.The residue is purified on a silica column (heptane).

Orange-coloured oil. m=24 g. Y=67%. ¹H NMR (CDCl₃): 0.21 (6H, s), 0.99(9H, s), 1.29-1.34 (3H, t), 2.26-2.27 (3H, d), 4.19-4.27 (2H, q),5.95-6.01 (1H, d, J=15 Hz), 6.79-6.81 (1H, m), 6.93-6.94 (1H, t),7.06-7.10 (1H, dd), 7.18-7.21 (1H, d), 7.68-7.79 (1H, q).

g) Ethyl 5-[3-(tert-butyldimethylsilanyloxy)phenyl]-hexanoate.

In a reactor, 15 g (43.3 mmol) of ethyl5-[3-(tert-butyldimethylsilanyloxy)phenyl]hexa-2,4-dienoate aredissolved in 200 ml of ethyl acetate and 800 mg of 5% palladium/carbonare added. The solution is stirred at room temperature and under ahydrogen pressure of 4 bar. 2 hours later, it is filtered on celite andevaporated. The residue is purified on a silica column (ethyl acetate3-heptane 97).

Yellow oil. m=11.7 g. Y=77%. ¹H NMR (CDCl₃): 0.08 (6H, s), 0.79 (9H, s),1.01-1.07 (6H, t), 1.32-1.39 (4H, m), 2.03-2.08 (2H, m), 2.40-2.45 (1H,m), 3.86-3.95 (2H, q), 6.45-6.48 (2H, m), 6.56-6.59 (1H, d, J=7.6 Hz),6.90-6.97 (1H, t).

h) 6-[3-(tert-Butyldimethylsilanyloxy)phenyl]-2-methylheptan-2-ol.

In a manner similar to Example 1(i), by reacting 55 ml (165 mmol) ofmethylmagnesium bromide 3M/ether with 11.6 g (33 mmol) of ethyl5-[3-tert-butyldimethylsilanyloxy)phenyl]hexanoate in 100 ml of ether, ayellow oil (m=10.65 g; Y=96%) is obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.79 (9H, s), 1.01, (3H, s), 1.03-1.08(3H, d), 1.20-1.39 (6H, m), 2.40-2.48 (1H, m), 6.45-6.47 (2H, m),6.56-6.59 (1H, d, J=7.6 Hz), 6.90-6.97 (1H, t).

i) 3-(5-Hydroxy-1,5-dimethylhexyl)phenol.

38 ml of tetrabutylammonium fluoride 1M/THF are added to 10.6 g (31.5mmol) of 6-[3-(tert-butyldimethylsilanyloxy)phenyl]-2-methylheptan-2-olin 100 ml of THF. The solution is stirred at room temperature. 2 hourslater, the solvent is evaporated. The residue is taken up in ethyl etherand washed with water. The organic phase is dried over magnesiumsulphate and concentrated. The product is purified on a silica column(ethyl acetate 25-heptane 75).

Yellow oil. m=6 g. Y=85%. ¹H NMR (CDCl₃): 1.17 (6H, s), 1.20-1.23 (3H,d), 1.40-1.66 (6H, m), 2.60-2.69 (1H, m), 5.19 (1H, OH, s), 6.62-6.66(2H, m), 6.73-6.76 (1H, d, J=7.7 Hz), 7.11-7.17 (1H, t).

j)6-[3-(3-Ethoxymethoxy-5-ethoxymethoxymethylbenzyloxy)phenyl]-2-methylheptan-2-ol.

A solution of 514 mg (2.3 mmol) of3-(5-hydroxy-1,5-dimethylhexyl)phenol, 81 mg (2.5 mmol) of sodiumhydride 75% in 10 ml of dimethylformamide is stirred for 30 minutes atroom temperature. 700 mg (2.1 mmol) of1-bromomethyl-3-ethoxymethoxy-5-ethoxymethoxymethylbenzene in 5 ml ofdimethylformamide are then added. The medium is stirred overnight atroom temperature. It is then poured into water and extracted with ether.The organic phase is dried over magnesium sulphate and concentrated. Theproduct is purified on a silica column (ethyl acetate 25-heptane 75).

Yellow oil. m=871 mg. Y=87%. ¹H NMR (CDCl₃): 1.15 (6H, s), 1.19-1.24(6H, m), 1.39-1.55 (4H, m), 2.62-2.71 (2H, m), 3.61-3.77 (4H, m), 4.59(2H, s), 4.76 (2H, s), 5.00 (2H, s), 5.23 (2H, s), 6.77-6.80 (3H, m),6.99 (1H, s), 7.05-7.08 (2H, d), 7.17-7.23 (1H, t).

k)3-[3-(5-Hydroxy-1,5-dimethylhexyl)phenoxymethyl]-5-hydroxymethylphenol.

In a manner similar to Example 1(j), by reacting 0.4 ml of concentratedsulphuric acid in 5 ml of methanol with 860 mg (1.8 mmol) of6-[3-(3-ethoxymethoxy-5-ethoxymethoxymethylbenzyloxy)phenyl]-2-methylheptan-2-olin 5 ml of methanol and 5 ml of THF, after purification on a silicacolumn (ethyl acetate 60-heptane 40), a colourless oil (m=510 mg. Y=79%)is obtained.

¹H NMR (CDCl₃): 1.14 (6H, s), 1.20-1.23 (3H, d), 1.34-1.57 (6H, m), 2.30(1H, OH, s), 2.61-2.69 (1H, m), 4.60 (2H, s), 5.02 (2H, s), 6.73-6.78(5H, s), 6.91 (1H, s), 7.14-7.20 (1H, t)

EXAMPLE 46-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol

a) (2-Hydroxymethyl-5-iodophenyl)methanol.

A solution of 2.55 g (37 mmol) of sodium nitrite in 10 ml of water isadded, dropwise, at 0° C., to 5 g (27.6 mmol) of 4-aminophthalic acid in30 ml of 20% sulphuric acid. This solution is added to 7.26 g (43.7mmol) of potassium iodide, 7.35 g (38.6 mmol) of copper iodide in 30 mlof 20% sulphuric acid. The stirring is continued for 2 hours at roomtemperature and then for 3 hours at 50° C. The medium is then pouredinto ethyl acetate. It is extracted with a saturated aqueous sodiumthiosulphate solution and then with a saturated aqueous sodium hydrogencarbonate solution. The aqueous phase is then acidified withhydrochloric acid up to pH 1 and extracted with ethyl acetate. Theorganic phase is dried over magnesium sulphate and concentrated. Theproduct obtained is dissolved in anhydrous THF and cooled to 0° C. 110ml of borane 1M/THF are added dropwise. 3 hours later, a solution of 250ml of a THF/water mixture (1/1) is added very slowly. After decantation,the aqueous phase is extracted with ether. The organic phase is washedseveral times with water and then dried over magnesium sulphate andconcentrated. The residue is purified on a silica column (ethyl acetate80-heptane 20).

Colourless oil. m=4.9 g. Y=69%. ¹H NMR (DMSO): 4.56-4.61 (4H, m),5.25-5.35 (2H, OH, m), 7.28-7.31 (1H, d, J=8 Hz), 7.68-7.72 (1H, dd,J=6.5 Hz, J′=1.5 Hz), 7.84 (1H, s)

b)4-iodo-1-(tert-Butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)phenyl.

In a manner similar to Example 3(c), by reacting 3.86 g (14.6 mmol) of(2-hydroxymethyl-5-iodophenyl)methanol with 5.08 ml of triethylamine,4.63 g (30.7 mmol) of tert-butyldimethylsilane chloride and 95 mg (0.78mmol) of dimethylaminopyridine in 30 ml of dimethylformamide, acolourless oil (m=7 g. Y=98%) is obtained.

c)4-(tert-Butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)benzaldehyde.

6.3 ml (15.75 mmol) of n-butyllithium 2.5 M/hexane are added, dropwise,at −78° C., to 7 g (14.2 mmol) of4-iodo-1-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)phenylin 50 ml of THF. 10 minutes later, 1.2 ml (15.6 mmol) of anhydrousdimethylformamide are added. The mixture is allowed to return to roomtemperature over 1 hour. Water and ether are then added. Afterdecantation, the ethereal phase is extracted with a saturated aqueousammonium chloride solution and then with water. The organic phase isdried over magnesium sulphate and concentrated. The residue is purifiedon a silica column (dichloromethane 50-heptane 50).

Yellowish solid. m=3.07 g. Y=55%. ¹H NMR (CDCl₃): 0.00 (12H, s), 0.83(18H, s), 4.64 (2H, s), 4.69 (2H, s), 7.52-7.56 (1H, d, J=7.8 Hz),7.66-7.70 (1H, dd, J=7.8 Hz, J′=1.4 Hz), 7.80 (1H, s), 9.89 (1H, s).

d)[4-(tert-Butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)phenyl]methanol.

In a manner similar to Example 3(a), by reacting 290 mg (7.6 mmol) ofsodium borohydride with 3 g (7.6 mmol) of4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)benzaldehydein 30 ml of methanol and 20 ml of THF, after purification on a silicacolumn (ethyl acetate 20-heptane 80), a yellow oil (m=2.6 g; Y=87%) isobtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.01 (6H, s), 0.843 (9H, s), 0.849 (9H,s), 4.58-4.60 (2H, d, J=5.8 Hz), 4.651 (2H, s), 4.659 (2H, s), 7.15-7.18(1H, m), 7.31-7.33 (2H, m).

e)4-Bromomethyl-1-(tert-butyldimethylsilanyloxy)-2-(tert-butyldimethylsilanyloxymethyl)benzene

In a manner similar to Example 3(b), by reacting 4.2 ml (9.4 mmol) oftrioctylphosphine, 3.1 g (9.4 mmol) of carbon tetrabromide with 1.7 g(4.3 mmol) of[4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)phenyl]methanolin 30 ml of ethyl ether, after purification on a silica column (AcOEt10-Heptane 90), a yellow oil (m=1.7 g; Y=86%) is obtained.

f)6-[3-(tert-Butyldimethylsilanyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol.

In a manner similar to Example 1(i), by reacting 31 ml (93 mmol) ofmethylmagnesium bromide 3M/ether with 8 g (23 mmol) of ethyl5-[3-tert-butyldimethylsilanyloxy)phenyl]hexa-2,4-dienoate in 100 ml ofether, after purification on a silica column (dichloromethane 70-heptane30), a yellow oil (m=4.6 g; Y=60%) is obtained.

¹H NMR (CDCl₃): 0.20 (6H, s), 0.99 (9H, s), 1.39 (6H, s), 2.15 (3H, s),5.92-5.98 (1H, d, J=15.1 Hz), 6.38-6.42 (1H, d, J=10.9 Hz), 6.58-6.68(1H, q), 6.73-6.74 (1H, dd), 6.89-6.90 (1H, t), 7.01-7.04 (1H, dd),7.14-7.20 (1H, t).

g) 3-(5-Hydroxy-1,5-dimethylhexa-1,3-dienyl)phenol.

In a manner similar to Example 3(i), by reacting 16 ml oftetrabutylammonium fluoride 1M/THF with 4.5 g (13.5 mmol) of6-[3-(tert-butyldimethylsilanyloxy)phenyl]-2-methylhepta-3,5-dien-2-olin 50 ml of THF, after purification on a silica column (ethyl acetate30-heptane 70), a yellow oil (m=2.2 g; Y=74%) is obtained.

¹H NMR (CDCl₃): 1.38 (6H, s), 2.32 (3H, s), 5.90-5.96 (1H, d, J=15 Hz),6.39-6.44 (1H, d, J=11.5 Hz), 6.57-6.68 (1H, q), 6.73-6.76 (1H, dd),6.91-6.94 (2H, m), 7.11-7.17 (1H, t), 8.36 (1H, s).

h)6-{3-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)benzyloxy]phenyl}-2-methylhepta-3,5-dien-2-ol.

In a manner similar to Example 3(j), by reacting 218 mg (1 mmol) of3-(5-hydroxy-1,5-dimethylhexa-1,3-dienyl)phenol, 39 mg (1.2 mmol) of 75%sodium hydride in 5 ml of dimethylformamide with 460 mg (1 mmol) of4-bromomethyl-1-(tert-butyldimethylsilanyloxy)-2-(tert-butyldimethylsilanyloxymethyl)benzenein 5 ml of dimethylformamide, after purification on a silica column(ethyl acetate 20-heptane 70), a yellow oil (m=440 mg, Y=74%) isobtained.

¹H NMR (CDCl₃): −0.007 (6H, s), 0.000 (6H, s), 0.84 (18H, s), 1.29 (3H,s), 4.65-4.66 (4H, d), 4.98 (2H, s), 5.82-5.88 (1H, d), 6.31-6.35 (1H,d), 6.49-6.59 (1H, m), 6.93-6.96 (2H, m), 7.10-7.13 (1H, d), 7.21-7.24(1H, d), 7.32-7.36 (1H, d), 7.41 (1H, s).

i)6-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol.

In a manner similar to Example 3(i), by reacting 1.6 ml oftetrabutylammonium fluoride 1M/THF with 424 mg (0.71 mmol) of6-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)benzyloxy]phenyl}-2-methylhepta-3,5-dien-2-olin 15 ml of THF, after purification on a silica column (ethyl acetate90-heptane 10), a yellow oil (m=206 mg; Y=79%) is obtained.

¹H NMR (CDCl₃): 1.38 (6H, s), 2.15 (3H, s), 4.33-4.35 (2H, m), 4.70-4.74(2H, m), 5.07 (2H, s), 5.92-5.98 (1H, d, J=15 Hz), 6.40-6.44 (1H, d,J=10.9 Hz), 6.58-6.68 (1H, q), 6.82-6.85 (1h, d, J=6.2 Hz), 7.03-7.05(2H, m), 7.19-7.26 (1H, m), 7.37 (2H, s), 7.45 (1H, s).

EXAMPLE 56-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylhexan-2-ol

a)3-Bromo-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)benzyloxy]phenyl.

In a manner similar to Example 3(j), by reacting 260 mg (1.5 mmol) of3-bromophenol, 58 mg (1.8 mmol) of 75% sodium hydride in 5 ml ofdimethylformamide with 690 mg (1.5 mmol) of4-bromomethyl-1-(tert-butyldimethylsilanyloxy)-2-(tert-butyldimethylsilanyloxymethyl)benzenein 10 ml of dimethylformamide, after purification on a silica column(ethyl acetate 7-heptane 93), a yellow oil (m=790 mg; Y=95%) isobtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 4.65-4.66 (4H, d), 4.95(2H, s), 6.78-6.81 (1H, dd), 6.97-7.07 (3H, m), 7.16-7.18 (1H, d),7.33-7.39 (2H, m).

b) Methyl5-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)benzyloxy]phenyl}pentanoate.

In a manner similar to Example 1(h), by reacting 780 mg (1.4 mmol) of3-bromo-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)benzyloxy]phenyl in10 ml of dimethylformamide with the solution, at 0° C., of 750 mg (3mmol) of 9-borabicyclo[3.3.1]nonane and 230 mg (2 mmol) of methylpent-4-enoate in 20 ml of THF, after purification on a silica column(ethyl acetate 5-heptane 95), a yellow oil (m=515 mg; Y=62%) isobtained.

¹H NMR (CDCl₃): 0.000 (s, 6H), 0.006 (s, 6H), 0.84 (s, 18H), 1.55-1.58(m, 4H), 2.21-2.24 (t, 2H), 2.50-2.53 (t, 2H), 3.57 (s, 3H), 4.65-4.66(d, 4H), 4.95 (s, 2H), 6.66-6.71 (m, 3H), 7.06-7.12 (t, 1H), 7.21-7.24(d, 1H), 7.31-7.36 (d, 1H), 7.40 (s, 1H).

c)6-{3-[3,4-bis-(tert-Butyldimethylsislanyloxymethyl)benzyloxy]phenyl}-2-methylhexan-2-ol.

In a manner similar to Example 1(I), by reacting 1.4 ml (4.2 mmol) ofmethylmagnesium bromide 3M/ether with 509 mg (0.87 mmol) of5-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)benzyloxy]-phenyl}pentanoatein 15 ml of ether, a yellow oil (m=503 mg; Y=99%) is obtained.

¹H NMR (CDCl₃): 0.000 (s, 6H); 0.005 (s, 6H); 0.847 (s, 18H); 1.115 (s,6H); 1.29-1.56 (m, 6H); 2.47-2.54 (t, 2H); 4.65 (s, 2H); 4.66 (s, 2H);4.95 (s, 2H); 6.67-6.72 (m, 3H); 7.06-7.12 (t, 1H); 7.21-7.24 (d, 1H);7.32-7.40 (m, 2H).

d) 6-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylhexan-2-ol.

In a manner similar to Example 3(I), by reacting 2 ml oftetrabutylammonium fluoride 1M/THF with 490 mg (0.83 mmol) of6-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)benzyloxy]phenyl}-2-methylhexan-2-olin 15 ml of THF, after purification on a silica column (ethyl acetate90-heptane 10), a yellow oil (m=196 mg; Y=66%) is obtained.

¹H NMR ¹H (CDCl₃): 1.17 (s, 6H); 1.31-1.64 (m, 4H); 2.56-2.62 (t, 2H);3.16-3.18 (m, 2H); 4.71 (s, 2H); 4.72 (s, 2H); 5.05 (s, 2H); 6.77-6.79(m, 3H); 7.15-7.21 (m, 1H); 7.35-7.41 (m, 3H).

EXAMPLE 66-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-2-methylheptan-2-ol

a) 4-Aminophthalic Acid

1 g (4.73 mmol) of 4-nitrophthalic acid is dissolved in 10 ml ofanhydrous ethanol. The solution is stirred at room temperature anddegassed under argon. 50 mg of 5% palladium/carbon are added all at onceand hydrogen is bubbled through the solution. After 3 hours, thesolution is filtered on celite and then evaporated.

Orange-coloured oil. m=820 mg. Y=96%. ¹H NMR (DMSO): 3.32 (1H, s), 5.95(1H, s), 6.49-6.53 (2H, m), 7.46-7.50 (1H, d, J=8.8 Hz), 12.33 (2H,COOH, s).

b) Dimethyl 4-Hydroxyphthalate.

A solution of 5 g (27.6 mmol) of 4-aminophthalic acid in 50 ml of 1Msulphuric acid is cooled to 0° C. and a solution of 2.27 g of sodiumnitrite in 6 ml of water is then slowly added. After 15 minutes at 0°C., 15 ml of concentrated sulphuric acid are added and the mixture isheated at 100° C., with vigorous stirring, for 1 hour. At roomtemperature, the reaction medium is extracted with ethyl acetate andwashed with water. After decantation, the organic phase is dried overmagnesium sulphate and concentrated. The residue is purified on a silicacolumn (dichloromethane 80-methanol 20). It is then dissolved in 100 mlof methanol and refluxed with 2 ml of acetic acid. After thedisappearance of the diacid, the methanol is evaporated and the productis taken up in ethyl acetate and washed with water.

M=5.2 g. Y=90%. ¹H NMR (DMSO): 3.64 (3H, s), 3.67 (3H, s), 6.79-6.86(2H, m), 7.56-7.60 (1H, d, J=8.4 Hz), 10.51 (1H, OH, s).

c) 1-(3-Chloromethylphenyl)ethanone.

30 ml of methyllithium are added, dropwise, at 0° C., to 4 g (23.4 mmol)of 3-chloromethylbenzoic acid in 250 ml of anhydrous ethyl ether. At theend of the addition, the solution is again stirred at 0° C. for 30minutes. Water is then slowly added and then the mixture is acidifiedwith hydrochloric acid. The organic phase is washed several times withwater, dried over magnesium sulphate and then concentrated. The residueis purified on a silica column (ethyl acetate 5-heptane 95).

M=2.7 g. Y=69%. ¹H NMR (CDCl₃): 2.62 (3H, s), 4.63 (2H, s), 7.44-7.50(1H, t), 7.59-7.62 (1H, d, J=7.6 Hz), 7.89-7.93 (1H, d, J=6.5 Hz), 7.97(1H, s).

d) 2-(3-Chloromethylphenyl)-2-methyl][1,3]dioxolane.

In a three-necked flask equipped with a Dean-Stark system, 2.5 g (14.8mmol) of 1-(3-chloromethylphenyl)ethanone are dissolved in 20 ml oftoluene. 4 ml (74 mmol) of ethylene glycol and 250 mg (1.48 mmol) ofpara-toluenesulphonic acid are added. The mixture is heated under refluxovernight. 200 mg of potassium carbonate are added and the medium ispoured into water and extracted with dichloromethane. The organic phaseis dried over magnesium sulphate and concentrated. The product ispurified on a silica column (ethyl acetate 10-heptane 90).

Oil. m=1.9 g. Y=59%. ¹H NMR (CDCl₃): 1.65 (3H, s), 3.71-3.84 (2H, m),3.97-4.11 (2H, m), 4.59 (2H, s), 7.32-7.37 (2H, m), 7.42-7.46 (1H, m),7.50 (1H, s).

e) 4-[3-(2-Methyl-[1,3]dioxolan-2-yl)benzyloxy)phthalate.

A solution of 1.83 g (8.6 mmol) of2-(3-chloromethylphenyl)-2-methyl-[1,3]dioxolane, 1.9 g (9.03 mmol) ofdimethyl 4-hydroxyphthalate, 1.25 g (9.03 mmol) of potassium carbonateand 200 mg of potassium iodide in 75 ml of 2-butanone is heated underreflux. After 3 hours and at room temperature, the mixture is filtered,concentrated and purified on a silica column (ethyl acetate 20-heptane80).

Colourless oil. m=3.2 g. Y=97%. ¹H NMR (CDCl₃): 1.66 (3H, s), 3.70-3.84(2H, m), 3.87 (3H, s), 3.91 (3H, s), 4.01-4.11 (2H, m), 5.12 (2H, s),7.04-7.08 (1H, dd, J=6 Hz, J′=2.6 Hz), 7.16-7.17 (1H, d, J=2.5 Hz),7.35-7.41 (2H, m), 7.45-7.49 (1H, m), 7.53 (1H, s), 7.79-7.82 (1H, d,J=8.6 Hz).

f){2-Hydroxymethyl-5-[3-(2-methyl-[1,3]dioxolan-2-yl)benzyloxy]phenyl}methanol.

3.2 g (8.3 mmol) of dimethyl4-[3-(2-methyl-[1,3]-dioxolan-2-yl)benzyloxy)phthalate are dissolved in10 ml of THF and 3 ml of toluene. 460 mg (21 mmol) of lithiumborohydride are then added and the mixture is heated under reflux for 1hour 30 minutes. The reaction medium is evaporated and taken up inwater, acidified with 1N hydrochloric acid and then extracted with ethylacetate. The organic phase is dried over magnesium sulphate andconcentrated.

Colourless oil. m=2.7 g. Y=99%. ¹H NMR (CDCl₃): 1.66 (3H, s), 3.74-3.80(2H, m), 4.01-4.10 (2H, m), 5.07 (2H, s), 6.90 (1H, m), 6.99 (1H, m),7.22 (1H, m), 7.35-7.37 (2H, m), 7.45 (1H, m), 7.54 (1H, s).

g) 1-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]ethanone.

2.7 g (8.3 mmol) of(2-hydroxymethyl-5-[3-(2-methyl-[1,3]dioxolan-2-yl)-benzyloxyl]phenyl}-methanoland 200 mg (0.8 mmol) of pyridinium para-toluenesulphonic in 5 ml ofwater and 20 ml of acetone are heated under reflux for 6 hours. At roomtemperature, the mixture is taken up in ethyl acetate and washed with asaturated aqueous sodium bicarbonate solution. The organic phase isdried over magnesium sulphate and concentrated.

h)1-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}ethanone.

In a manner similar to Example 3(c), by reacting 3 g (20 mmol) oftert-butyldimethylsilane chloride with 2.3 g (8 mmol) of1-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]ethanone, 50 mg ofdimethylaminopyridine in 3.5 ml (24 mmol) of triethylamine and 50 ml ofdimethylformamide, 3 g of a colourless oil are obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.01 (6H, s), 0.84 (9H, s), 0.86 (9H, s),2.54 (3H, s), 4.57 (2H, s), 4.68 (2H, s), 5.05 (2H, s), 6.72-6.77 (1H,dd, J=5.7 Hz, J′=2.6 Hz), 7.06-7.07 (1H, d, J=2.6 Hz), 7.17-7.20 (1H,m), 7.37-7.43 (1H, t), 7.56-7.59 (1H, d, J=7.6 Hz), 7.82-7.85 (1H, d,J=7.8 Hz), 7.94 (1H, s).

i) Ethyl5-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}hexa-2,4-dienoate.

2.48 ml (11 mmol) of ethyl 4-(diethoxyphosphoryl)but-2-enoate in 5 ml ofTHF are added, at 0° C., to a solution of 360 mg (11.25 mmol) of sodiumhydride in 5 ml of THF and 10 ml of1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone. The mixture isstirred at 0° C. for 1 hour and then 2.89 g (5.6 mmol) of1-{3-(3,4-bis-tert-butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}ethanonein 20 ml of THF are added dropwise. The mixture is kept stirring at roomtemperature for 24 hours. Water is then added and the mixture isacidified with 1N hydrochloric acid and extracted with dichloromethane.The organic phase is washed with water, dried over sodium sulphate andconcentrated. The residue is purified on a silica column (ethyl acetate5-heptane 95).

Oil. m=1.2 g. Y=36%. ¹H NMR (CDCl₃): 0.00 (6H, s), 0.01 (6H, s), 0.84(9H, s), 0.86 (9H, s), 1.19 (3H, s), 1.21-1.27 (3H, t), 4.57 (2H, s),4.68 (2H, s), 5.01 (2H, s), 5.88-5.94 (1H, d, J=15 Hz), 6.48-6.53 (1H,d, J=11.6 Hz), 6.74-6.77 (1H, dd, J=8.3 Hz). 7.08 (1H, d), 7.17-7.20(2H, m), 7.31 (2H, m), 7.47 (1H, s), 7.62-7.72 (1H, q).

j) Ethyl5-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}hexanoate

350 mg of 5% rhodium/alumina are added to 750 mg (1.22 mmol) of ethyl5-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}-hexa-2,4-dienoatein 50 ml of ethyl acetate. Hydrogen is bubbled through the medium for 1hour 30 minutes. The mixture is then filtered on celite andconcentrated.

Colourless oil. m=665 mg. Y=88%.

k)6-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 1(i), by reacting 0.53 ml (1.6 mmol) ofmethylmagnesium bromide with 320 mg (0.52 mmol) of ethyl5-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]-phenyl}hexanoatein 10 ml of THF, after purification on a silica column (ethyl acetate10-heptane 90), a colourless oil (m=265 mg; Y=85%) is obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.01 (6H, s), 0.85 (9H, s), 0.87 (9H, s),1.08 (6H, s), 1.15-1.18 (3H, d), 1.15-1.48 (6H, m), 2.63-2.66 (1H, m),4.58 (2H, s), 4.68 (2H, s), 4.96 (2H, s), 6.73-6.77 (1H, dd, J=5.6 Hz,J′=2.6 Hz), 7.05-7.07 (2H, m), 7.16-7.23 (4H, m).

l) 6-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-2-methylheptan-2-ol.

In a manner similar to Example 3(i), by reacting 1.25 ml oftetrabutylammonium fluoride with 250 mg (0.41 mmol) of6-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}-2-methylheptan-2-olin 7 ml of THF, after purification on a silica column (ethyl acetate30-heptane 70), a colourless oil (m=130 mg; Y=85%) is obtained.

¹H NMR (CDCl₃): 1.11 (6H, s), 1.22-1.25 (3H, d), 1.16-1.42 (4H, m),1.51-1.60 (2H, q), 2.66-2.74 (1H, m), 4.63 (2H, s), 4.65 (2H, s), 5.07(2H, s), 6.83-6.88 (1H, dd, J=5.6 Hz, J′=2.6 Hz), 6.97-6.98 (1H, d,J=2.5 Hz), 7.11-7.14 (1H, d, J=7.26 Hz), 7.20-7.32 (4H, m).

EXAMPLE 77-[3-{3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-3-ethyloctan-3-ol

a)7-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}-3-ethyloctan-3-ol.

In a manner similar to Example 1(i), by reacting 370 mg (0.6 mmol) ofethyl5-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]-phenyl}hexanoatewith 1.8 ml (1.8 mmol) of ethylmagnesium bromide, a colourless oil(m=265 mg; Y=70%) is obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.01 (6H, s), 0.70-0.76 (6H, t), 0.84 (9H,s), 0.87 (9H, s), 1.15-1.18 (3H, d), 1.15-1.53 (10H, m), 2.63-2.66 (1H,m), 4.58 (2H, s), 4.69 (2H, s), 4.96 (2H, s), 6.74-6.77 (1H, dd, J=5.6Hz, J′=2.6 Hz), 7.05-7.07 (2H, m), 7.16-7.22 (4H, m).

b) 7-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-3-ethyloctan-3-ol.

In a manner similar to Example 3(i), by reacting 230 mg (0.36 mmol) of7-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}-3-ethyloctan-3-olwith 1.2 ml of tetrabutylammonium fluoride, a colourless oil (m=110 mg;Y=75%) is obtained.

¹H NMR (CDCl₃): 0.75-0.81 (6H, t), 1.22-1.25 (3H, d), 1.22-1.69 (10H,m), 2.66-2.75 (1H, m), 4.64 (2H, s), 4.66 (2H, s), 5.07 (2H, s),6.84-6.89 (1H, dd, J=5.6 Hz, J′=2.6 Hz), 6.98-6,99 (1H, d, J=2.5 Hz),7.11-7.14 (1H, d, J=7.3 Hz), 7.21-7.32 (4H, m).

EXAMPLE 85-{2-[4-(5-Hydroxy-5-methylhexyl)phenyl]vinyl}-benzene-1,3-diol

a) 6-Bromo-2-methylhexan-2-ol.

340 ml (476 mmol) of methylmagnesium bromide 1.4 M/THF are added,dropwise, at −78° C., to a solution of 25 g (120 mmol) of ethyl5-bromovalerate in 150 ml of THF. The mixture is stirred for 3 hours ata temperature of between −78 and −30° C. At −30° C., a saturated aqueousammonium chloride solution is added slowly. At room temperature, themedium is extracted with ether. The ethereal phase is washed with water,dried over magnesium sulphate and concentrated. The residue is purifiedon a silica column (dichloromethane).

Yellow oil. m=21.5 g, Y=92%. ¹H NMR (CDCl₃): 1.23 (6H, s), 1.45-1.59(4H, m), 1.82-1.93 (2H, m), 3.40-3.45 (2H, t).

b) 2-(5-Bromo-1,1-dimethylpentyloxy)tetrahydropyran.

A solution of 21.5 g (0.11 mol) of 6-bromo-2-methylhexan-2-ol in 150-mlof ethyl ether with 15 ml (0.16 mol) of dihydropyran and 100 mg ofpara-toluenesulphonic acid is stirred overnight at room temperature. Asaturated aqueous sodium bicarbonate solution is then added and themixture is extracted with ether. The organic phase is washed with water,dried over sodium sulphate and concentrated. The residue is purified ona silica column (dichloromethane 70-heptane 30).

Yellow oil. m=29.2 g. Y=95%.

c) 7-Bromo-2-methylheptan-2-ol.

In a manner similar to Example 8(a), by reacting 160 ml (0.48 mol) ofmethylmagnesium bromide with 26.8 g (0.12 mol) of ethyl6-bromohexanoate, a yellowish oil (m=25.2 g; Y=100%) is obtained.

¹H NMR (CDCl₃): 1.21 (6H, s), 1.37-1.50 (6H, m), 1.82-1.93 (2H, m),3.39-3.44 (2H, t).

d) 2-(6-Bromo-1,1-dimethylhexyloxy)tetrahydropyran.

In a manner similar to Example 8(b), by reacting 14.11 g (0.168 mol) ofdihydropyran with 25.2 g (0.12 mol) of 7-bromo-2-methylheptan-2-ol, ayellowish oil (m=34.8 g; Y=90%). is obtained.

¹H NMR (CDCl₃): 1.18-1.20 (6H, d), 1.39-1.90 (14H, m), 3.38-3.44 (2H,t), 3.38-3.48 (1H, m), 3.92-3.96 (1H, m), 4.69-4.71 (1H, d).

e) Ethyl (4-Bromobenzyl)phosphonate.

A solution of 25 g (0.1 mol) of 4-bromobenzyl bromide and 19 ml (0.11mol) of triethylphosphite is heated at 100° C. for 24 hours. At roomtemperature, the residue is purified on a silica column (dichloromethaneand then ethyl acetate).

Yellow oil. m=31 g. Y=100%. ¹H NMR (CDCl₃): 1.22-1.28 (6H, t), 3.05-3.13(2H, d), 3.96-4.08 (4H, q), 7.15-7.19 (2H, dd, J=6 Hz, J′=2.4 Hz),7.42-7.45 (2H, d, J=8 Hz).

f) 3-(Tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)benzaldehyde.

30.25 ml (0.33 mol) of dihydropyran are added, dropwise, to a solutionof 11.5 g (0.083 mol) of 3,5-dihydroxybenzaldehyde and 1.05 g (4.18mmol) of pyridinium para-toluenesulphonate in 250 ml of dichloromethane.The mixture is stirred for 2 hours at room temperature. The reactionmedium is poured into a saturated aqueous sodium hydrogen carbonatesolution. The organic phase is washed with water, dried over magnesiumsulphate and concentrated. The residue is purified on a silica column(dichloromethane).

Yellow oil. m=22.8 g. Y=90%. ¹H NMR (CDCl₃): 1.57-1.71 (6H, m),1.83-2.06 (6H, m), 3.60-3.65 (2H, m), 3.83-3.93 (2H, m), 5.46-5.49 (2H,m), 7.02 (1H, s), 7.20-7.21 (2H, c), 9.90 (1H, s).

g) Ethyl (3-Bromobenzyl)phosphonate.

In a manner similar to Example 8(e), by reacting 25.2 g (0.1 mol) of3-bromobenzyl bromide with 19 ml (0.11 mol) of triethylphosphite, ayellowish oil (m=32.6 g; Y=100%) is obtained.

¹H NMR (CDCl₃): 1.26-1.31 (6H, t), 3.06-3.15 (2H, d), 3.97-4.09 (4H, q),7.14-7.23 (2H, m), 7.36-7.44 (2H, m).

h)4-Bromo-{2-[3-(tetrahydropyran-2-yl-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl.

In a manner similar to Example 1(g), by reacting 157 mg (5.2 mmol) ofsodium hydride with a solution of 1.32 g (4.3 mmol) of3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)benzaldehyde and1.59 g (5.2 mmol) of ethyl (4-bromobenzyl)phosphonate in 30 ml of THF,after purification on a silica column (dichloromethane 60-heptane 40), ayellowish oil (m=1.78 g; Y=90%) is obtained. m.p.=77-9° C.

¹H NMR (CDCl₃): 1.57-1.76 (6H, m), 1.83-2.07 (6H, m), 3.60-3.65 (2H, m),3.88-3.97 (2H, m), 5.44-5.45 (2H, d), 6.72 (1H, s), 6.86 (2H, s), 6.99(2H, s), 7.32-7.35 (2H, d, J=8.5 Hz), 7.44-7.47 (2H, d, J=8.4 Hz).

i)3-Bromo-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl.

In a manner similar to Example 1(g), by reacting 3.08 g (0.01 mol) of3-tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)benzaldehyde and 3.68g (0.12 mol) of ethyl (3-bromobenzyl)phosphonate with 362 mg (0.012 mol)of sodium hydride, a yellowish oil (m=4.43; Y=96%) is obtained.

¹H NMR (CDCl₃): 1.58-1.77 (6H, m), 1.83-2.07 (6H, m), 3.61-3.65 (2H, m),3.88-3.97 (2H, m), 5.44-5.45 (2H, m), 6.72 (1H, s), 6.86 (2H, s),6.92-7.06 (2H, q), 7.17-7.23 (1H, m), 7.34-7.40 (2H, m), 7.63 (1H, s).

j)2-[5-(4-{2-[3-(Tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)-1,1-dimethylpentyloxy]tetrahydropyran.

2.17 g (7.8 mmol) of 2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyranare added, at 35° C., to a solution of 208 mg (8.6 mmol) of magnesium in8 ml of anhydrous THF with an iodine crystal. The magnesium compound isheated at 35° C. for 4 hours. At room temperature, 1.43 g (3.11 mmol) of4-bromo-{2-[3-(tetrahydropyran-2-yl}-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl,63 mg (0.12 mmol) of (1,2-bis(diphenylphosphino)ethane]dichloronickeland 6 ml of anhydrous ether are added and the mixture is heated at 35°C. overnight. The reaction medium is poured into a saturated aqueousammonium chloride solution and extracted with ether. The organic phaseis washed with water, dried over magnesium sulphate and concentrated.The product is purified on a silica column (ethyl acetate 10-heptane90).

Yellowish oil. m=1.75 g. Y=97%. ¹H NMR (CDCl₃): 1.18-1.20 (6H, d), 1.26(6H, s), 1.37-2.05 (24H, m), 2.58-2.64 (2H, t), 3.40-3.45 (1H, m),3.60-3.65 (2H, m), 3.90-3.97 (3H, m), 4.68 (1H, m), 5.44-5.46 (2H, d),6.69 (1H, s), 6.86 (2H, s), 6.93-7.09 (2H, q), 7.14-7.17 (2H, d, J=8Hz), 7.38-7.41 (2H, d, J=8 Hz).

k) 5-{2-[4-(5-Hydroxy-5-methylhexyl)phenyl]vinyl}-benzene-1,3-diol.

A solution of 1.74 g (3 mmol) of2-[5-(4-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl-1,1-dimethylpentyloxy]tetrahydropyranin 50 ml of acetic acid, 25 ml of THF and 12 ml of water is stirredovernight at room temperature. It is then evaporated to dryness and theresidue thus obtained is triturated in a mixture of ethyl ether andhexane. After filtration, the product is dried.

White crystals. m=423 mg. Y=55%. m.p.=177-8° C. ¹H NMR (DMSO): 1.23 (6H,s), 1.53 (4H, m), 1.72 (2H, m), 2.72-2.75 (2H, t), 4.24 (1H, OH, s),6.33 (1H, s), 6.61 (2H, s), 7.17 (2H, s), 7.34-7.37 (2H, d, J=7.6 Hz),7.64-7.67 (2H, d, J=7.7 Hz), 9.42 (2H, OH, s).

EXAMPLE 9 5-{2-[4-(5-Hydroxy-5-methylhexyl)phenyl]ethyl}benzene-1,3-diol

414 mg (1.27 mmol) of5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol in 40 mlof dioxane and 42 mg of 10% palladium/carbon are placed in a reactor. Ahydrogen pressure of 7 bar is exerted for 4 hours at room temperature.The reaction medium is filtered on celite and the filtrate isevaporated. The product is crystallized from an ethyl acetate/hexanemixture.

Whitish powder m=227 mg. Y=69%. m.p.=144-5° C. ¹H NMR (CDCl₃): 1.19 (6H,s), 1.28-1.66 (6H, m), 2.55-2.61 (2H, t), 2.72-2.83 (4H, m), 6.20-6.24(3H, m), 7.07 (4H, s), 8.12 (2H, OH, s).

EXAMPLE 105-{2-[4-(6-Hydroxy-6-methylheptyl)phenyl]vinylbenzene-1,3-diol

a)2-[6-(4-{2-[3-(Tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyran.

In a manner similar to Example 8(j), by reacting 4.33 g (9.42 mmol) of4-bromo-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenylin 12 ml of ether with the solution of 630 mg (26 mmol) of magnesium, 7g (23.8 mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 20ml of THF and catalysed with 193 mg (0.36 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, a yellowish oil (m=5g; Y=90%) is obtained.

¹H NMR (CDCl₃): 1.18-1.20 (6H, d), 1.26-1.63 (20H, m), 1.84-1.87 (4H,m), 1.97-2.01 (2H, m), 2.57-2.63 (2H, t), 3.41-3.45 (1H, m), 3.60-3.65(2H, m), 3.90-3.97 (3H, m), 4.69 (1H, m), 5.45-5.46 (2H, m), 6.69 (1H,s), 6.86 (2H, s), 6.93-7.09 (2H, q), 7.13-7.17 (2H, d, J=8 Hz),7.38-7.41 (2H, d, J=8 Hz).

b) 5-{2-[4-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}-benzene-1,3-diol.

In a manner similar to Example 8(k), by reacting 4.98 g (8.4 mmol) of2-[6-(4-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]-vinyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyranwith the solution of 100 ml of acetic acid, 50 ml of THF and 25 ml ofwater, whitish crystals (m=1.85 g; Y=65%) are obtained. m.p.=158-60° C.

¹H NMR (CDCl₃): 1.19 (6H, s), 1.35-1.43 (6H, m), 1.63 (2H, m), 2.08 (1H,OH, s), 2.56-2.62 (2H, t), 6.33 (1H, s), 6.52-6.53 (2H, d), 6.86-7.03(2H, q), 7.12-7.15 (2H, d, J=8 Hz), 7.36-7.39 (2H, d, J=8 Hz), 8.40 (2H,OH, s).

EXAMPLE 115-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}-benzene-1,3-diol

a)2-[6-(3-{2-[3-(Tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl}-1,1-dimethylhexyloxy]tetrahydropyran

In a manner similar to Example 8(j), by reacting 4.39 g (9.56 mmol) of3-bromo-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)pheny]vinyl}phenylin 12 ml of ether with the solution of 630 mg (26 mmol) of magnesium, 7g (23.8 mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 20ml of THF and catalysed by 193 mg (0.36 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, a yellowish oil(m=4.5 g; Y=79%) is obtained.

¹H NMR (CDCl₃): 1.18-1.20 (6H, d), 1.26-1.67 (20H, m), 1.84-1.87 (4H,m), 2.01 (2H, m), 2.58-2.64 (2H, t), 3.41-3.45 (1H, m), 3.61-3.65 (2H,m), 3.90-3.97 (3H, m), 4.69 (1H, m), 5.45-5.46 (2H, m), 6.70 (1H, s),6.87 (2H, s), 6.96-7.08 (3H, m), 7.21-7.30 (3H, m).

b) 5-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}-benzene-1,3-diol.

In a manner similar to Example 8(k), by reacting 4.50 g (7.6 mmol) of2-[6-(3-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]-vinyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyranwith the solution of 100 ml of acetic acid, 50 ml of THF and 25 ml ofwater, and after purification on a silica column (ethyl acetate50-heptane 50), beige crystals (m=1.23 g; Y=48%) are obtained.m.p.=98-100° C.

¹H NMR (CDCl₃): 1.20 (6H, s), 1.35-1.44 (6H, m), 1.64-1.67 (2H, m),2.57-2.63 (2H, t), 6.35 (1H, s), 6.55 (2H, s),. 6.96-6.97 (2H, d),7.03-7.06 (1H, d, J=6.6 Hz), 7.19-7.29 (3H, m), 8.22 (2H, OH, s).

EXAMPLE 125-{2-[4-(6-Hydroxy-6-methylheptyl)phenyl]ethyl}benzene-1,3-diol

In a manner similar to Example 9(a), by reacting 1 g (2.9 mmol) of5-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol with 100mg of 10% palladium/carbon, whitish crystals (m=728 mg; Y=91%) areobtained. m.p.=128-30° C.

¹H NMR (CDCl₃): 1.19 (6H, s), 1.33-1.42 (6H, m), 1.61-1.63 (2H, m), 1.99(1H, OH, s), 2.53-2.59 (2H, t), 2.73-2.86 (4H, m), 6.24 (3H, s),7.05-7.12 (4H, dd, J=8.8 Hz), 8.08 2H, OH, s).

EXAMPLE 135-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]ethyl)benzene-1,3-diol

In a manner similar to Example 9(a), by reacting 600 mg (1.76 mmol) of5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol with 60mg of 10% palladium/carbon, pinkish crystals (m=368 mg; Y=61%) areobtained. m.p.=102-3° C.

¹H NMR (CDCl₃): 1.20 (6H, s), 1.23-1.56 (8H, m), 1.99 (1H, OH, s),2.46-2.52 (2H, t), 2.74-2.82 (4H, m), 6.14-6.18 (3H, m), 6.47 (2H, OH,s), 6.79 (1H, s), 6.92-697 (2H, m), 7.11-7.17 (1H, t).

EXAMPLE 142-Hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol

a) 4-Bromo-2-hydroxymethylphenol.

In a manner similar to Example 3(a), by reacting 190 mg (5 mmol) ofsodium borohydride with 1 g (5 mmol) of 5-bromosalicylilaldehyde in 10ml of methanol and 15 ml of THF, beige crystals (m=900 mg; Y=89%) areobtained.

¹H NMR (CDCl₃)+DMSO) 4.47 (1H, OH, s), 4.71 (2H, s), 6.73-6.76 (1H, d,J=9.2 Hz), 7.19-7.22 (2H, m), 8.82 (1H, OH, s).

b) 6-Bromo-2,2-dimethyl-4H-benzo[1,3]dioxin.

59 ml (0.48 mol) of dimethoxypropane and 2 g (0.01 mol) ofpara-toluenesulphonic acid are added to 42.5 g (0.2 mol) of4-bromo-2-hydroxymethylphenol in 400 ml of dimethylformamide. Thereaction medium is stirred overnight at room temperature. It is pouredinto ice-cold water and extracted with ether. The organic phase is driedover magnesium sulphate and concentrated. The product is purified on asilica column (dichloromethane).

Yellow oil. m=47.2 g. Y=93%. ¹H NMR (CDCl₃): 1.52 (6H, s), 4.80 (2H, s),6.68-6.72 (1H, d, J=8.7 Hz), 7.09-7.10 (1H, d, J=2.2 Hz), 7.22-7.27 (1H,m).

c) 2,2-Dimethyl-4H-benzo[1,3]dioxin-6-carbaldehyde.

In a manner similar to Example 4(c), by reacting 49 ml of n-butyllithium2.5 M/hexane, at −78° C., with 27 g (111 mmol) of6-bromo-2,2-dimethyl-4H-benzo[1,3]dioxin in 200 ml of THF and 30 minuteslater, with 8.5 ml (111 mmol) of dimethylformamide, after purificationon a silica column (dichloromethane 70-heptane 30), white crystals(m=7.7 g; Y=36%) are obtained. (Low yield, the product very rapidlybecomes degraded). m.p.=49-51° C.

¹H NMR (CDCl₃): 1.57 (6H, s), 4.90 (2H, s), 6.91-6.94 (1H, d, J=8.4 Hz),7.55 (1H, t), 7.68-7.72 (1H, dd, J=6.5 Hz, J′=1.9 Hz).

d) 6-[2-(3-Bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin.

In a manner similar to Example 1(g), by reacting 78 mg (2.59 mmol) ofsodium hydride with 410 mg (2.14 mmol) of2,2-dimethyl-4H-benzo[1,3]dioxin-6-carbaldehyde and 775 mg (2.52 mmol)of ethyl (3-bromobenzyl)phosphonate in 20 ml of THF, yellowish crystals(m=596 mg; Y=81%) are obtained. m.p.=128-9° C.

¹H NMR (CDCl₃): 1.56 (6H, s), 4.87 (2H, s), 6.80-6.89 (2H, m), 6.98-7.04(1H, d, J=16.3 Hz), 7.11 (1H, s), 7.16-7.22 (1H, m), 7.31-7.38 (3H, m),7.62 (1H, s).

e)2,2-Dimethyl-6-(2-{3-[5-methyl-5-(tetrahydropyran-2-yloxy)hexyl]phenyl}vinyl)-4H-benzo[1,3]dioxin.

In a manner similar to Example 8(j), by reacting 500 mg (1.45 mmol) of6-[2-(3-bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin in 2 ml ofether with the solution of 97 mg (4 mmol) of magnesium, 2.02 g (7.24mmol) of 2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyran in 7 ml of THFand catalysed by 31 mg (0.058 mmol) of[1,2-bis(diphenylphosphino)ethane]dichloronickel, a yellow oil (m=323mg; Y=48%) is obtained.

¹H NMR (CDCl₃): 1.19-1.21 (6H, d), 1.56 (6H, s), 1.48-1.82 (12H, m),2.60-2.66 (2H, t), 3.43-3.45 (1H, m), 3.91 (1H, m), 4.69 (1H, m), 4.87(2H, s), 6.79-6.83 (1H, d, J=8.4 Hz), 6.96-6.99 (1H, d, J=7.2 Hz),7.05-7.07 (1H, d, J=4.95 Hz), 7.12 (1H, s), 7.21-7.35 (4H, m).

f) 2-Hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol.

In a manner similar to Example 8(k), by reacting 313 mg (0.67 mmol) of2,2-dimethyl-6-(2-{3-[5-methyl-5-(tetrahydropyran-2-yloxy)hexyl]phenyl}vinyl)-4H-benzo[1.3]dioxinin 10 ml of acetic acid, 5 ml of THF and 2.5 ml of water, and afterpurification on a silica column (ethyl acetate 40-heptane 60), whitecrystals (m=91 mg; Y=40%) are obtained. m.p.=130-1° C.

¹H NMR (CDCl₃): 1.01 (6H, s), 1.32 (4H, m), 1.51 (2H, m), 2.50-2.56 (2H,t), 4.04 (1H, OH, s), 4.44-4.46 (2H, d, J=4.4 Hz), 4.98 (1H, OH, m),6.70-6.74 (1H, d, J=8.3 Hz), 6.88-7.34 (7H, m), 7.50 (1H, s), 9.51 (1H,OH,

EXAMPLE 152-Hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}-phenol

a) 6-[2-(4-Bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin.

In a manner similar to Example 1(g), by reacting 188 mg (6.24 mmol) ofsodium hydride with 1 g (5.2 mmol) of2,2-dimethyl-4H-benzo[1,3]dioxin-6-carbaldehyde and 1.52 g (5.2 mmol ofethyl (4-bromobenzyl)phosphonate in 10 ml of THF, a white solid (m=1.4g; Y=78%) is obtained.

¹H NMR (CDCl₃): 1.55 (6H, s), 4.86 (2H, s), 6.79-6.96 (3H, m), 7.03 (1H,s), 7.30-7.33 (3H, m), 7.43-7.46 (2H, d, J=8.5 Hz).

b)2,2-Dimethyl-6-(2-{4-[5-methyl-5-(tetrahydropyran-2-yloxy)hexyl]phenyl]}vinyl)-4H-benzo[1,3]-dioxin.

In a manner similar to Example 8(j) by reacting 500 mg (1.45 mmol) of6-[2-(4-bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin in 2 ml ofether with the solution of 97 mg (4 mmol) of magnesium, 2.02 g (7.24mmol) of 2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyran in 7 ml of THFand catalysed by 31 mg (0.058 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, a yellowish solid(m=654 mg; Y=97%) is obtained. m.p.=86-7° C.

¹H NMR (CDCl₃): 1.18-1.20 (6H, d), 1.50-1.83 (18H, m), 2.58-2.61 (2H,t), 3.45 (1H, m), 3.93 (1H, m), 4.71 (1H, m), 4.87 (2H, m), 6.79-6.82(1H, m), 6.96 (2H, m), 7.12-7.17 (3H, m), 7.31-7.40 (3H, m).

c) 2-Hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol.

In a manner similar to Example 8(k), by reacting 640 mg (1.38 mmol) of2,2-dimethyl-6-(2-{4-[5-methyl-5-tetrahydropyran-2-yloxy)hexyl]phenyl]}vinyl)-4H-benzo[1,3]dioxinin 24 ml of the solution (20 ml of acetic acid+10 ml of THF+5 ml ofwater), a white powder (m=140 mg; r=50%) is obtained. m.p.=139-40° C.

¹H NMR (DMSO): 1.11 (6H, s), 1.42 (4H, m), 1.60 (2H, m), 2.57-2.63 (2H,t), 4.14 (1H, s), 4.55-4.57 (2H, d, J=4.6 Hz), 5.09 (1H, OH, m),6.81-6.84 (1H, d, J=8.3 Hz), 6.98-7.14 (2H, m), 7.21-7.24 (2H, d, J=8.1Hz), 7.32-7.35 (1H, d, J=8.9 Hz), 7.50-7.53 (2H, d, J=7.8 Hz), 7.60 (1H,s), 9.61 (1H, s).

EXAMPLE 162-Hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol

a)2,2-Dimethyl-6-(2-{3-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]phenyl}vinyl)-4H-benzo[1,3]dioxin.

In a manner similar to Example 8(j), by reacting 467 mg (1.35 mmol) of6-[2-(3-bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin in 2 ml ofether with the solution of 90 mg (3.71 mmol) of magnesium, 990 mg (3.37mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 3.5 ml ofTHF and catalysed by 29 mg (0.05 mmol) of[1,2-bis(diphenylphosphino)ethane]dichloronickel, a yellowish oil (m=363mg; Y=56%) is obtained.

¹H NMR (CDCl₃): 1.18-1.20 (6H, d), 1.56 (6H, s), 1.35-1.83 (14H, m),2.58-2.64 (2H, t), 3.41-3.45 (1H, m), 3.92-3.96 (1H, m), 4.69 (1H, m),4.87 (2H, s), 6.79-6.83 (1H, d, J=8.5 Hz), 6.90-7.04 (2H, dd, J=16.3 Hz,J′=7.4 Hz), 7.04-7.07 (1H, m), 7.13 (1H, s), 7.21-7.35 (4H, m).

b)2-Hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol.

In a manner similar to Example 8(k), by reacting 350 mg (0.73 mmol) of2,2-dimethyl-6-(2-{3-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]phenyl}vinyl)-4H-benzo[1,3]dioxinin 15 ml of the solution (20 ml of acetic acid+10 ml of THF+5 ml ofwater), a whitish powder (m=165 mg; Y=70%) is obtained. m.p.=120-22° C.

¹H NMR (DMSO): 0.85 (6H, s), 1.12 (6H, m), 1.40 (2H, m), 2.35-2.41 (2H,t), 3.87 (1H, OH, s), 4.29-4.31 (2H, d, J=4.8 Hz), 4.83 (1H, t),6.55-6.59 (1H, d, J=8.2 Hz), 6.73-7.18 (7H, m), 7.35 (1H, s), 9.36 (1H,s).

EXAMPLE 172-Hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol

a)2,2-Dimethyl-6-(2-{4-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]phenyl}vinyl)-4H-benzo[1,3]dioxin.

In a manner similar to Example 8(j), by reacting 467 mg (1.35 mmol) of6-[2-(4-bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin in 2 ml ofether with the solution of 90 mg (3.71 mmol) of magnesium, 990 mg (3.37mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 3.5 ml ofTHF and catalysed by 29 mg (0.05 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, whitish crystals(m=563 mg; Y=87%) are obtained.

m.p.=72° C. ¹H NMR (CDCl₃): 1.18-1.20 (6H, d), 1.55 (6H, s), 1.25-1.83(14H, m), 2.56-2.63 (2H, t), 3.41-3.45 (1H, m), 3.92-3.96 (1H, m),4.69-4.71 (1H, m), 4.87 (2H, s), 6.79-6.82 (1H, d, J=8.5 Hz), 6.88-7.02(2H, dd, J=16.4 Hz, J′=2.3 Hz), 7.11-7.16 (3H, m), 7.30-7.33 (1H, d,J=8.5 Hz), 7.37-7.40 (2H, d, J=8.1 Hz).

b)2-Hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol.

In a manner similar to Example 8(k), by reacting 548 mg (1.14 mmol) of2,2-dimethyl-6-(2-{4-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]-phenyl}vinyl)-4H-benzo[1,3]dioxinin 20 ml of the solution (20 ml of acetic acid+10 ml of THF+5 ml ofwater), a white powder (m=290 mg; Y=72%) is obtained. m.p.=145-6° C.

¹H NMR (DMSO): 0.87 (6H, s), 1.13 (6H, m), 1.39 (2H, m), 2.37-2.40 (2H,t), 3.88 (1H, OH, s), 4.30-4.32 (2H, d, J=5.1 Hz), 4.83-4.85 (1H, t),6.57-6.6 (1H, d, J=8.25 Hz), 6.74-6.89 (2H, m), 6.96-6.99 (2H, d, J=8.2Hz), 7.07-7.11 (1H, d, J=8.3 Hz), 7.26-7.29 (2H, d, J=8 Hz), 7.35 (1H,s), 9.36 (1H, s).

EXAMPLE 182-Hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylheptyl)phenyl]ethyl}phenol

In a manner similar to Example 9(a), by reacting 50 mg (0.147 mmol) of2-hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenolwith 10 mg of 10% palladium/carbon, whitish crystals (m=26 mg; Y=52%)are obtained. m.p.=101-4° C.

¹H NMR (DMSO): 0.93 (6H, s), 1.23 (4H, m), 1.40 (2H, m), 2.39-2.44 (6H,m), 3.96 (1H, OH, s), 4.32-4/34 (2H, d), 4.78-4.83 (1H, t), 6.51-6.55(1H, d, J=8.1 Hz), 6.74-7.07 (6H, m), 8.97 (1H, OH, s).

EXAMPLE 192-Hydroxy-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]-ethyl}phenol

In a manner similar to Example 9(a), by reacting 110 mg (0.32 mmol) of2-hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenolwith 30 mg of 10% palladium/carbon, crystals (m=81 mg; Y=74%) areobtained. m.p.=124-6° C.

¹H NMR (DMSO): 1.12 (6H, s), 1.42 (4H, m), 1.59 (2H, m), 2.58 (6H, m),4.52-4.54 (2H, d), 4/98-5.03 (1H, OH, t), 5.84 (1H, s), 6.71-6.74 (1H,d, J=8.1 Hz), 6.94-6.97 (1H, d, J=8.3 Hz), 7.14-7.24 (5H, m), 9.17 (1H,OH, s).

EXAMPLE 202-Hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol

In a manner similar to Example 9(a), by reacting 97 mg (0.27 mmol) of2-hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenolwith 27 mg of 10% palladium/carbon, yellowish crystals (m=70 mg; Y=73%)are obtained. m.p.=73-5° C.

¹H NMR (CDCl₃): 1.21 (6H, s), 1.23-1.61 (8H, m), 2.51-2.57 (3H, t), 2.82(4H, s), 4.80 (2H, s), 6.75-7.00 (6H, m), 7.15-7.21 (1H, t), 7.36 (1H,OH, s).

EXAMPLE 212-Hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol

In a manner similar to Example 9(a), by reacting 150 mg (0.42 mmol) of2-hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenolwith 42 mg of 10% palladium/carbon, crystals (m=65 mg; Y=43%) areobtained. m.p.=110-1° C.

¹H NMR (DMSO): 0.85 (6H, s), 1.10 (6H, m), 1.34 (2H, m), 2.29-2.35 (6H,m), 3.86 (1H, s), 4.24-4.26 (2H, d), 4.70-4.74 (1H, t), 6.43-6.46 (1H,d, J=8.09 Hz), 6.66-6.70 (1H, d, J=8.1 Hz), 6.86-6.96 (5H, s), 8.89 (1H,s).

EXAMPLE 222-Hydroxymethyl-5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol

a) 2-Hydroxy-4-iodobenzoic Acid.

40 g (1 mol) of sodium hydroxide are added to 55.6 g (0.2 mol) of methyl4-iodosalicylate in 600 ml of THF, 10 ml of methanol and 10 ml of water.The solution is heated at 40° C. overnight. It is then evaporated. Theresidue is taken up in water. It is acidified to pH 1 with concentratedhydrochloric acid and extracted with ethyl acetate. The organic phase iswashed several times with water, dried over magnesium sulphate andconcentrated. The product is triturated in a dichloromethane-hexanemixture and then filtered.

Orange-coloured powder. m=48.53 g. Y=92%. ¹H NMR (CDCl₃): 7.20-7.24 (1H,dd, J=6.8 Hz, J′=1.5 Hz), 7.36-7.37 (1H, d, J=1.5 Hz), 7.52-7.56 (1H, d,J=8.3 Hz), 11.29 (1H, s).

b) 5-Hydroxymethyl-5-iodophenol.

In a manner similar to Example 1(c), by reacting 300 ml of borane 1M THFwith 48.45 g (0.183 mol) of 2-hydroxy-4-iodobenzoic acid in one liter ofTHF, after purification on a silica column (dichloromethane and thenethyl acetate), beige crystals (m=26.82 g; Y=59%) are obtained.

¹H NMR (CDCl₃): 4.69 (2H, s), 6.80-6.83 (1H, d, J=7.9 Hz), 7.12-7.16(1H, dd, J=6.3 Hz, J′=1.6 Hz), 7.21-7.22 (1H, d, J=1.6 Hz), 8.94 (1H,s).

c) 7-iodo-2,2-Dimethyl-4H-benzo[1,3]dioxin.

In a manner similar to Example 14(b), by reacting 22.7 g (0.218 mol) of2,2-dimethoxypropane, 554 mg (2.9 mmol) of para-toluenesulphonic acidwith 24.25 g (0.097 mol) of 5-hydroxymethyl-5-iodophenol in 500 ml ofDMF, after purification on a silica column (dichloromethane 50-heptane50), white crystals (m=21.88 g; Y=78%) are obtained. m.p.=50-2° C.

¹H NMR (CDCl₃): 1.52 (6H, s), 4.77 (2H, s), 6.70 (1H, m), 7.19-7.22 (2H,m).

d) 2,2-Dimethyl-4H-benzo[1,3]dioxin-7-carbaldehyde.

In a manner similar to Example 4(c), by reacting 31 ml of n-butyllithium2.5 M/hexane, at −78° C., with 20.4 g (70 mmol) of7-iodo-2,2-dimethyl-4H-benzo[1,3]dioxin in 300 ml of THF and, 30 minuteslater, with 6 ml (77 mmol of dimethylformamide, after purification on asilica column (dichloromethane 60-heptane 40), yellowish crystals(m=10.38 g; Y=85%) are obtained. m.p.=53-4° C.

¹H NMR (CDCl₃): 1.56 (6H, s), 4.90 (2H, s), 7.11-7.14 (1H, d, J=7.8 Hz),7.31-7.32 (1H, d, J=1.26 Hz), 7.40-7.44 (1H, dd, J=6.4 Hz, J′=1.4 Hz),9.91 (1H,

e) 7-[2-(4-Bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin.

In a manner similar to Example 1(g), by reacting 724 mg (24 mmol) ofsodium hydride with 3.84 g (20 mmol) of2,2-dimethyl-4H-benzo[1,3]dioxin-7-carbaldehyde and 7.37 g (24 mmol) ofethyl (4-bromobenzyl)phosphonate in 110 ml of THF, a white solid (m=6.5g; Y=.94%) is obtained. m.p.=137-9° C.

¹H NMR (CDCl₃): 1.55 (6H, s), 4.85 (2H, s), 6.93-7.05 (5H, m), 7.32-7.35(2H, d, J=8.5 Hz), 7.44-7.47 (2H, d, J=8.5 Hz).

f)2,2-Dimethyl-7-(2-{4-[5-methyl-5-(tetrahydropyran-2-yloxy)hexyl]phenyl}vinyl)-4H-benzo[1,3]dioxin.

In a manner similar to Example 8 (j), by reacting 1.7 g (4.9 mmol) of7-[2-(4-bromophenyl)vinyl]-2,2-dimethyl-4H-benzo[1,3]dioxin in 6 ml ofether with the solution of 330 mg (13.5 mmol) of magnesium, 3.43 g (12.3mmol) of 2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyran in 12 ml ofTHF and catalysed by 105 mg (0.199 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 10-heptane 90), white crystals (m=2.02 g;Y=89%) are obtained. m.p.=70-4° C.

¹H NMR (CDCl₃): 1.11-1.14 (6H, d), 1.49 (6H, s), 1.19-1.76 (12H, m),2.52-2.58 (2H, t), 3.34-3.38 (1H, m), 3.85-3.89 (1H, m), 4.62-4.64 (1H,m), 4.78 (2H, s), 6.85-7.02 (6H, m), 7.08-7.11 (2H, d, J=8 Hz),7.32-7.35 (2H, d, J=8 Hz).

g) 2-Hydroxymethyl-5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol.

In a manner similar to Example 8(k), by reacting 2 g (4.3 mmol) of2,2-dimethyl-7-(2-{4-[5-methyl-5-(tetrahydropyran-2-yloxy)hexyl]phenyl}vinyl-4H-benzo[1,3]dioxinin a solution of 50 ml of acetic acid+25 ml of THF+12.5 ml of water,after purification on a silica column (ethyl acetate 50-heptane 50), awhite powder (m=44 mg; Y=3%) is obtained. m.p.=163-5° C.

¹H NMR (DMSO): 0.87 (6H, s), 1.18 (4H, m), 1.36 (2H, m), 2.40 (2H, t),3.89 (1H, s), 4.30 (2H, s), 6.77 (1H, s), 6.88 (3H, m), 6.99-7.02 (2H,d, J=7.6 Hz), 7.08-7.11 (1H, d, J=7.9 Hz), 7.30-7.33 (2H, d, J=7.8 Hz),9.24 (1H, s).

EXAMPLE 236-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylheptan-2-ol

a)6-{3-[3-(tert-Butyldimethylsilanyloxymethyl)-4-(1,1,2,2-tetramethylpropoxymethyl)benzyloxy]phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 3(j), by reacting 24 mg (0.1 mmol) of3-(5-hydroxy-1,5-dimethylhexyl)phenol, 3.4 mg (0.11 mmol) of 80% sodiumhydride in 2 ml of dimethylformamide with 50 mg (0.1 mmol) of4-bromomethyl-1-(tert-butyldimethylsilanyloxy)-2-(tert-butyldimethylsilanyloxymethyl)benzenein 4 ml of dimethylformamide, after purification on a silica column(ethyl acetate 20-heptane 80), a yellow oil (m=50 mg; Y=77%) isobtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 1.06 (6H, s), 1.11-1.14(3H, d), 1.19-1.48 (6H, m), 2.56-2.58 (1H, m), 4.65 (2H, s), 4.66 (2H,s), 4.95 (2H, s), 6.67-6.71 (3H, m), 7.07-7.13 (1H, m), 7.21-7.25 (1H,d, J=8.4 Hz), 7.32-7.35 (1H, d, J=7.8 Hz), 7.41 (1H, s).

b) 6-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylheptan-2-ol.

In a manner similar to Example 3(i), by reacting 50 mg (0.08 mmol) of6-{3-[3-(tert-butyldimethylsilanyloxymethyl)-4-(1,1,2,2-tetramethylpropoxymethyl)benzyloxy]phenyl}-2-methylheptan-2-olwith 0.17 ml of tetrabutylammonium fluoride 1M/THF, a colourless oil(m=29 mg; Y=94%) is obtained.

¹H NMR (CDCl₃): 1.11 (6H, s), 1.20-1.23 (3H, d), 1.33-1.56 (6H, m),2.60-2.69 (1H, m), 3.64 (2H, OH, s), 4.66 (4H, s), 5.04 (2H, s),6.76-6.78 (3H, m), 7.15-7.38 (4H, m).

EXAMPLE 244-[3-(5-Hydroxy-1,5-dimethylhexyl)phenoxymethyl]-2-hydroxymethylphenol

a) (2,2-Dimethyl-4H-benzo[1,3]dioxin-6-yl)methanol.

In a manner similar to Example 3(a), by reacting 115 mg (3 mmol) ofsodium borohydride with 580 mg (3 mmol) of2,2-dimethyl-4H-benzol[1,3]dioxin-6-carbaldehyde in 15 ml of methanoland 10 ml of THF, after purification on a silica column (ethyl acetate30-heptane 70), a white solid (m=500 mg; Y=85%) is obtained. m.p.=42-4°C.

b) 6-Bromomethyl-2,2-dimethyl-4H-benzo[1,3]dioxin.

In a manner similar to Example 3(b), by reacting 2.5 ml (5.6 mmol) oftrioctylphosphine, 1.9 g (5.6 mmol) of carbon tetrabromide with 500 mg(2.6 mmol) of (2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)methanol in 20 mlof ethyl ether, after purification on a silica column (AcOEt 8-heptane92), a colourless oil (m=445 mg; Y=67%) is obtained.

c)6-[3-(2,2-Dimethyl-4H-benzo[1,3]dioxin-6-ylmethoxy)phenyl]-2-methylheptan-2-ol.

In a manner similar to Example 3(j), by reacting 44 mg (0.2 mmol) of3-(5-hydroxy-1,5-dimethylhexyl)phenol, 6.2 mg (0.22 mmol) of 80% sodiumhydride in 5 ml of dimethylformamide with 52 mg (0.2 mmol) of6-bromomethyl-2,2-dimethyl-4H-benzo[1,3]dioxin in 5 ml ofdimethylformamide, after purification on a silica column (ethyl acetate20-heptane 80), a colourless oil (m=43 mg; Y=55%) is obtained.

¹H NMR (CDCl₃): 1.15 (6H, s), 1.21-1.23 (3H, d), 1.23-1.54 (6H, m), 2.65(1H, m), 4.86 (2H, s), 4.93 (2H, s), 2H, s), 6.78-6.85 (4H, m), 7.07(1H, s), 7.20-7.26 (2H, m).

d)4-[3-(5-Hydroxy-1,5-dimethylhexyl)phenoxymethyl]-2-hydroxymethylphenol.

In a manner similar to Example 8(k), by reacting 43 mg (0.1 mmol) of6-[3-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-ylmethoxy)phenyl]-2-methylheptan-2-olin 2 ml of the solution (5 ml of acetic acid+2.5 ml of THF+1.25 ml ofwater), a colourless oil (m=12 mg; Y=31%) is obtained.

¹H NMR (CDCl₃): 1.12 (6H, s), 1.19-1.22 (3H, d), 1.32-1.56 (6H, m),2.59-2.68 (1H, m), 4.81 (2H, s), 4.96 (2H, s), 6.74-6.79 (3H, m),6.85-6.89 (1H, d, J=8.2 Hz), 7.07 (1H, s), 7.15-7.22 (2H, m), 7.69 (1H,OH, s).

EXAMPLE 256-{3-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol

a)3-Bromo-[2-{3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl}vinyl]phenyl.

In a manner similar to Example 1(g), by reacting 53 mg (1.8 mmol) ofsodium hydride with 600 mg (1.5 mmol) of4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)benzaldehydeand 560 mg (1.8 mmol) of ethyl (3-bromobenzyl)phosphonate in 30 ml ofTHF, a colourless oil (m=830 mg; Y=100%) is obtained.

¹H NMR (CDCl₃): 0.00, (6H, s), 0.02 (6H, s), 0.84 (9H, s), 086 (9H, s),4.64 (2H, s), 4.66 (2H, s), 6.86-7.04 (2H, dd, J=16.3 Hz, J′=11.6 Hz),7.08-7.14 (1H, m), 7.24-7.32 (4H, m), 7.48 (1H, s), 7.55 (1H, s).

b)2-[5-(3-{3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylpentyloxy]-tetrahydropyran.

In a manner similar to Example 8(j), by reacting 236 mg (0.43 mmol) of3-bromo-[2-{3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl}vinyl]-phenylin 1 ml of ether with the solution of 29 mg (1.18 mmol) of magnesium,300 mg (1.07 mmol) of 2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyranin 2 ml of THF and catalysed by 10 mg (0.019 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a yellowish oil (m=34 mg;Y=12%) is obtained.

¹H NMR (CDCl₃): −0.02 (6H, s), 0.00 (6H, s), 0.82 (9H, s), 0.84 (9H, s),0.84 (9H, s), 1.06-1.08 (6H, d), 1.13-1.70 (12H, m), 2.48-2.54 (2H, t),3.27-3.36 (2H, m), 3.79 (1H, m), 4.62 (2H, s), 4.64 (2H, s), 6.93-6.97(3H, m), 7.10-7.19 (3H, m), 7.27 (2H, s), 7.46 (1H, s).

c)[2-Hydroxymethyl-5-(2-{3-[5-methyl-5-(tetrahydropyran-2-yloxy)hexyl]phenyl}vinyl)phenyl]methanol.

In a manner similar to Example 3(i), by reacting 67 mg (0.1 mmol) of2-[5-(3-{3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylpentyloxy]tetrahydropyranwith 0.2 ml of tetrabutylammonium fluoride 1M/THF, a yellowish oil (m=44mg; Y=100%) is obtained.

¹H NMR (CDCl₃): 1.19-1.20 (6H, d), 1.43-1.82 (12H, m), 2.61-2.67 (2H,t), 3.42 (1H, m), 3:91 (1H, m), 4.69 (1H, m), 4.75 (2H, s), 4.78 (2H,s), 7.09 (3H, m), 7.26 (2H, m), 7.29-7.35 (2H, m), 7.42-7.45 (1H, m),7.51 (1H, s).

d)6-{3-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylhexan-2-ol.

0.09 ml of concentrated sulphuric acid are added to 44 mg (0.1 mmol) of[2-hydroxymethyl-5-(2-{3-[5-methyl-5-(tetrahydropyran-2-yloxy)hexyl]-phenyl}vinyl)phenyl]methanolin 1 ml of THF and 1 ml of water. The solution is heated at 40° C. for48 hours. Water is added and the mixture is extracted with ether. Theorganic phase is dried over magnesium sulphate and concentrated. Theproduct is triturated in an ether-hexane mixture and is then filteredand dried.

Whitish crystals. m=15 mg. Y=42%. m.p. 115-7° C. ¹H NMR (CDCl₃): 1.21(6H, s), 1.49-1.66 (6H, m), 2.62-2.65 (2H, t), 4.74 (2H, s), 4.77 (2H,s), 7.10-7.51 (9H, m).

EXAMPLE 267-{4-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol

a)4-Bromo-[2-{3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl}vinyl]phenyl.

In a manner similar to Example 1(g), by reacting 61 mg (2.03 mmol) ofsodium hydride with 667 mg (1.69 mmol) of4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)benzaldehydeand 623 mg (2.03 mmol) of ethyl (₄-bromobenzyl)phosphonate in 15 ml ofTHF, after purification on a silica column (dichloromethane 10-heptane90), white crystals (m=790 mg; Y=85%) are obtained. m.p.=80-1° C.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.02 (6H, s), 0.84 (9H, s), 0.86 (9H, s),4.64 (2H, s), 4.66 (2H, s), 6.88-7.04 (2H, q), 7.25-7.30 (4H, m),7.35-7.38 (2H, d), 7.48 (1H, s).

b)2-[6-(4-{2-[3,4-bis(tert-Butyldimethylsilanyloxy-methyl)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]-tetrahydropyran.

In a manner similar to Example 8(j), by reacting 390 mg (0.71 mmol) of4-bromo-[2-{3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl}vinyl]phenylin 1 ml of ether with the solution of 48 mg (1.96 mmol) of magnesium,520 mg (1.77 mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in2 ml of THF and catalysed by 15 mg (0.028 mmol) of[1,2-bis(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a yellowish oil (m=347 mg;Y=72%) is obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.02 (6H, s), 0.84 (9H, s), 0.87 (9H, s),1.08-1.10 (6H, d), 1.13-1.74 (14H, m), 2.48-2.54 (2H, t), 3.31-3.39 (1H,m), 3.82 (1H, m), 4.59 (1H, m), 4.64 (2H, s), 4.67 (2H, s), 6.97 (2H,s), 7.04-7.08 (2H, d, J=8 Hz), 7.29-7.34 (4H, m), 7.49 (1H, s).

c)7-{4-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 25(d), by reacting 5 drops ofconcentrated sulphuric acid with 335 mg (0.49 mmol) of2-[6-(4-{2-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyranin 5 ml of THF and 5 ml of water, white crystals (m=94 mg; Y=52%) areobtained. m.p. 112-4° C.

¹H NMR (CDCl₃): 1.20 (6H, s), 1.38 (6H, m), 1.64 (2H, m), 2.61 (2H, t),4.72 (2H, s), 4.75 (2H, s), 7.06-7.25 (4H, m), 7.347.49 (5H, m).

EXAMPLE 276-{4-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylhexan-2-ol

a)2-[5-(4-{2-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylpentyloxy]tetrahydropyran.

In a manner similar to Example 8(j), by reacting 375 mg (0.68 mmol) of4-bromo-[2-{3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl}vinyl]phenylin 1 ml of ether with the solution of 46 mg (1.88 mmol) of magnesium,478 mg (1.71 mmol) of 2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyranin 2 ml of THF and catalysed by 15 mg of (0.028 mmol) of[1,2-bis(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a yellowish oil (m=278 mg;Y=61%) is obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.02 (6H, s), 0.84 (9H, s), 0.86 (9H, s),1.08-1.10 (6H, d), 1.18-1.73 (12H, m), 2.49-2.55 (2H, t), 3.36-3.39 (1H,m), 3.81 (1H, m), 4.59 (1H, m), 4.64 (2H, s), 4.67 (2H, s), 6.97 (2H,s), 7.05-7.08 (2H, d, J=8 Hz), 7.29-7.34 (4H, m), 7.48 (1H, s).

b)6-{4-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylhexan-2-ol.

In a manner similar to Example 25(d), by reacting 10 drops ofconcentrated sulphuric acid with 265 mg (0.4 mmol) of2-[5-(4-{2-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylpentyloxy]tetrahydropyranin 5 ml of THF and 5 ml of water, white crystals (m=73 mg; Y=51%) areobtained. m.p.=102-4° C.

¹R NMR (CDCl₃): 1.20 (6H, s), 1.47 (4H, m), 1.63 (2H, m), 2.63 (2H, t),4.72 (2H, s), 4.74 (2H, s), 6.99-7.15 (2H, dd, J=16.5 Hz, J′=5 Hz),7.15-7.18 (2H, d, J=8 Hz), 7.31-7.34 (1H, m), 7.40-7.44 (3H, d, J=8 Hz),7.50 (1H, s).

EXAMPLE 285-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]-1-methylvinyl}benzene-1,3-diol

a) 1-[3,5-bis(tert-Butyldimethylsilanyloxy)phenyl]ethanone.

In a manner similar to Example 3(c), by reacting 34.7 g (0.22 mmol) oftert-butyldimethylsilane chloride with 15.68 g (0.1 mmol) of3,5-dihydroxyacetophenone at 611 mg of dimethylaminopyridine in 30.7 ml(0.22 mmol) of triethylamine and 160 ml of dimethylformamide, afterpurification on a silica column (ethyl acetate 10-heptane 90), an orangeoil (m=33 22 g; Y=87%) is obtained.

¹H NMR (CDCl₃): 0.01 (12H, s), 0.78 (18H, s), 2.33 (3H, s), 6.32-6.33(1H, t), 6.82 (1H, s), 6.83 (1H, s).

b)3-Bromo-{2-[3,5-bis(tert-butyldimethylsilanyloxy)phenyl]propenyl}phenyl.

In a manner similar to Example 1(g), by reacting 362 mg (12 mmol) ofsodium hydride with 3.8 g (10 mmol) of1-[3,5-bis(tert-butyldimethylsilanyloxy)phenyl]ethanone and 3.68 g (12mmol) of ethyl (3-bromobenzyl)phosphonate in 75 ml of THF, afterpurification on a silica column (ethyl acetate 10-heptane 90), crystalsare obtained (m=2.12 g; Y=52%).

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 2.03 (3H, d), 6.14 (3H,s), 6.22 (1H, s), 6.77-6.89 (2H, m), 7.00-7.08 (2H, m).

c)2-[6-(3-{2-[3,5-bis(tert-Butyldimethylsilanyloxy)phenyl]propenyl}phenyl)-1,1-dimethylhexyloxy]-tetrahydropyran.

In a manner similar to Example 8(j), by reacting 1.04 g (2 mmol) of3-bromo-{2-[3,5-bis(tert)-butyldimethylsilanyloxy)phenyl]propenyl}phenylin 2.5 ml of ether with the solution of 134 mg (5.5 mmol) of magnesium,1.47 g (5 mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 5ml of THF and catalysed by 43 mg (0.08 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a yellowish oil (m=1.08 g;Y=66%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.85 (18H,s), 1.10-1.76 (20H, m), 2.04(3H, d), 2.31-2.37 (2H, t), 3.36 (1H, m), 3.84 (1H, m), 4.62 (1H, m),6.14-6.31 (4H, m), 6.67-6.93 (4H, m).

d)7-(3-{2-[3,5-bis(tert-Butyldimethylsilanyloxy)phenyl]propenyl}phenyl)-2-methylheptan-2-ol.

In a manner similar to Example 25(d), by reacting 0.28 ml ofconcentrated sulphuric acid with 1.06 g (1.1 mmol) of2-[6-(3-{2-[3,5-bis(tert-butyldimethylsilanyloxy)phenyl]propenyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyranin 25 ml of THF and 25 ml of water, after purification on a silicacolumn (ethyl acetate 10-heptane 90), a yellow oil (m=420 mg; Y=43%) isobtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.85 (18H, s), 1.12 (6H, s), 1.19-1.51(8H, m), 2.04 (3H, d), 2.31-2.38 (2H, t), 6.14-6.19 (3H, m), 6.31 (1H,s), 6.68-6.79 (3H, m), 6.88-6.94 (1H, t).

e)5-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]-1-methylvinyl}benzene-1,3-diol.

In a manner similar to Example 3(i), by reacting 402 mg (0.69 mmol) of7-(3-{2-[3,5-bis(tert-butyldimethylsilanyloxy)phenyl]propenyl}phenyl)-2-methylheptan-2-olwith 1.4 ml of tetrabutylammonium fluoride 1M/THF, after purification ona silica column (ethyl acetate 40-heptane 60), white crystals (m=176 mg;Y=72%) are obtained. m.p. 113-4° C.

¹H NMR (CDCl₃): 1.20 (6H, s), 1.20-1.44 (8H, m), 2.12-2.13 (3H, d),2.33-2.39 (2H, t), 2.89 (1H, OH, s), 6.19-6.20 (2H, d, J=2 Hz),6.30-6.35 (2H, m), 6.80-6.90 (3H, m), 7.01-7.07 (1H, t), 7.98 (2H, OH,s).

EXAMPLE 295-{2-[3-(5-Hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol

a)2-[5-(3-{3,5-bis(Tetrahydropyran-2-yloxy)phenyl]-vinyl}phenyl)-1,1-dimethylpentyloxy]tetrahydropyran.

In a manner similar to Example 8(j), by reacting 2.59 g (5.64 mmol) of3-bromo-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenylin 7 ml of ether with the solution of 377 mg (15.5 mmol) of magnesium,3.94 g (14.1 mmol) of 2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyranin 14 ml of THF and catalysed by 121 mg (0.23 mmol) of[1,2-bis-(diphenylphosphino)ethane]-dichloronickel, after purificationon a silica column (ethyl acetate 10-heptane 90), a yellowish oil(m=2.65 g; Y=81%) is obtained.

¹H NMR (CDCl₃): 1.19-1.21 (6H, d), 1.48-1.63 (18H, m), 1.87-2.01 (6H,m), 2.60-2.66 (2H, t), 3.41-3.45 (1H, m), 3.61-3.65 (2H, m), 3.90-3.97(3H, m), 4.69 (1H, m), 5.45-5.46 (2H, d), 6.70 (1H, s), 6.87 (2H, s),7.03-7.08 (3H, m), 7.21-7.30 (3H, m).

b) 5-{2-[3-(5-Hydroxy-5-methylhexyl)phenyl]vinyl}-benzene-1,3-diol.

In a manner similar to Example 25(d), by reacting 0.75 ml ofconcentrated sulphuric acid with 2.58 g (4.46 mmol) of2-[5-(3-{3,5-bis(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)-1,1-dimethylpentyloxy]tetrahydropyranin 15 ml of THF and 15 ml of water, after purification on a silicacolumn (ethyl acetate 40-heptane 60), white crystals (m=680 mg; Y=47%)are obtained. m.p. 145-7° C.

¹H NMR (CDCl₃): 1.20 (6H, s), 1.31-1.64 (6H, m), 2.59-2.65 (2H, t), 2.83(1H, OH, s), 6.34 (1H, s), 6.54 (2H, s), 6.96 (2H, m), 7.04-7.06 (1H, d,J=7 Hz), 7.20-7.36 (3H, m), 8.64 (2H, OH, s).

EXAMPLE 30 5-[3-(6-Hydroxy-6-methylheptyl)phenoxymethyl]benzene-1,3-diol

a) Methyl 3,5-Dihydroxybenzoate.

In a manner similar to Example 1(a), by reacting 44 ml (0.8 mol) ofconcentrated sulphuric acid with 61.65 g (0.4 mol) of3,5-dihydroxybenzoic acid in 600 ml of methanol, a white powder (m=63.86g, Y=95%) is obtained. m.p.=162-3° C.

¹H NMR (CDCl₃): 3.85 (3H, s), 6.59-6.61 (1H, t), 7.02-7.03 (2H, d), 8.67(2H, s).

b) 3,5-bis(tert-Butyldimethylsilanyloxy)benzoate.

In a manner similar to Example 3(c), by reacting 126 9 (836 mmol) oftert-butyldimethylsilane chloride with 63.86 g (380 mmol) of methyl3,5-dihydroxybenzoate, 2.32 g of dimethylaminopyridine in 116.5 ml (836mmol) of triethylamine and 600 ml of dimethylformamide, afterpurification on a silica column (dichloromethane 30-heptane 90), ayellow oil (m=113.46 g; Y=75%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.78 (18H, s), 3.68 (3H, s), 6.31-6.32(1H, t), 6.91-6.92 (2H, d).

c) [3,5-bis(tert-Butyldimethylsilanyloxy)phenyl]-methanol.

In a manner similar to Example 1(e), by reacting 144 ml ofdiisobutylaluminium hydride 1M/toluene, at −78° C., with 18.86 g (47mmol) of methyl 3,5-bis(tert-butyldimethylsilanyloxy)benzoate, acolourless oil (m=16.97 g; Y=98%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.78 (18H, s), 4.36-4.38 (2H, d),6.05-6.07 (1H, t), 6.27-6.28 (2H, d).

d) 1-Bromomethyl-3,5-bis(tert-butyldimethylsilanyloxy)benzene.

In a manner similar to Example 3(b), by reacting 45.6 ml (92 mmol) oftrioctylphosphine, 33.56 g (101 mmol) of carbon tetrabromide with 16.95g (46 mmol) of [3,5-bis(tert-butyldimethylsilanyloxy)phenyl]methanol in300 ml of ethyl ether, after purification on a silica column(dichloromethane 10-heptane 90), a colourless oil (m=15.61 g; Y=79%) isobtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.78 (18H, s), 4.16 (2H, s), 6.05-6.07(1H, t), 6.28-6.29 (2H, d).

e) 3-Bromo-3,5-bis(tert-butyldimethylsilanyloxy)benzyloxy]phenyl.

1.04 g (7.5 mmol) of potassium carbonate and 166 mg (1 mmol) ofpotassium iodide are added to a solution of 865 mg (5 mmol) of3-bromophenol and 3.24 g (7.5 mmol) of1-bromomethyl-3,5-bis(tert-butyldimethylsislanyloxy)benzene in 80 ml of2-butanone. The reaction medium is heated for 6 hours under reflux andthen stirred at room temperature overnight. It is then poured into asaturated aqueous ammonium chloride solution and extracted with ether.The organic phase is washed with water, dried over magnesium sulphateand concentrated. The residue is purified on a silica column(dichloromethane 15-heptane 85).

Yellowish oil. m=1.09 g. Y=42%. ¹H NMR (CDCl₃): 0.00 (12H, s), 0.78(18H, s), 4.76 (2H, s), 6.09-6.11 (1H, t), 6.31-6.32 (2H, d), 6.67-6.71(1H, m), 6.87-6.98 (3H, m).

f)2-(6-[3-[3,5-bis(tert-Butyldimethylsilanyloxy)benzyloxy]phenyl}-1,1-dimethylhexyloxy)tetrahydropyran.

In a manner similar to Example 8(j), by reacting 1.06 g (2 mmol) of3-bromo[3,5-bis(tert-butyldimethylsilanyloxy)benzyloxy]phenyl in 2.5 mlof ether with the solution of 135 mg (5.56 mmol) of magnesium, 1.47 g (5mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 5 ml of THFand catalysed by 45 mg (85 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a yellow oil (m=793 mg;Y=60%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.79 (18H, s), 1.00-1.02 (6H, d),1.08-1.66 (14H, m), 2.35-2.42 (2H, t), 3.23-3.28 (1H, m), 3.74-3.78 (1H,m), 4.51 (1H, m), 4.76 (2H, s), 6.08-6.09 (1H, t), 6.34-6.35 (2H, d),6.57-6.60 (3H, m), 6.95-7.02 (1H, t).

g)5-{3-[6-Methyl-6-(tetrahydropyran-2-yloxy)heptyl]-phenoxymethyl}benzene-1,3-diol.

In a manner similar to Example 3(i), by reacting 777 mg (1.18 mmol) of2-(6-{3-[3,5-bis(tert-butyldimethylsilanyloxy)benzyloxy]phenyl}-1,1-dimethylhexyloxy)tetrahydropyranwith 2.4 ml of tetrabutylammonium fluoride 1M/THF, after purification ona silica column (ethyl acetate 30-heptane 70), a yellow oil (m=505 mg;Y=99%) is obtained.

¹H NMR (CDCl₃): 1.17-1.19 (6H, d), 1.29-1.84 (14H, m), 2.51-2.57 (2H,t), 3.50 (1H, m), 3.96 (1H, m), 4.73 (1H, m), 4.98 (2H, s), 6.29 (1H,s), 6.45 (2H, s), 6.72-6.75 (3H, m), 7.12-7.18 (1H, t).

h) 5-[3-(6-Hydroxy-6-methylheptyl)phenoxymethyl]-benzene-1,3-diol.

In a manner similar to Example 25(d), by reacting 0.07 ml ofconcentrated sulphuric acid with 505 mg (1.18 mmol) of5-{3-[6-methyl-6-tetrahydropyran-2-yloxy)heptyl]phenoxymethyl}benzene-1,3-diolin 4 ml of THF and 2 ml of water, after purification on a silica column(ethyl acetate 40-heptane 60), a yellowish paste (m=342 mg; Y=84%) isobtained.

¹H NMR (CDCl₃): 1.05 (6H, s), 1.30-1.55 (8H, m), 2.50 (2H, m), 4.07 (1H,OH, s), 4.89 (2H, s), 6.12 (1H, s), 6.26 (2H, s), 6.74-6.78 (3H, m),7.13-7.16 (1H, t).

EXAMPLE 315-{2-[3-(7-Hydroxy-7-methyloct-1-enyl)phenyl]vinyl}-benzene-1,3-diol

a) Methyl hept-6-Enoate.

320 mg (2.6 mmol) of dimethylaminopyridine and 8 ml (197 mmol) ofmethanol are added to 4 g (31.2 mmol) of heptenoic acid in 100 ml ofdichloromethane. The solution is cooled to 0° C., and 7.2 g (34.9 mmol)of N,N′-dicyclohexylcarbodiimide are added and the mixture is allowed toreturn to room temperature. After 5 h, the precipitate is filtered, thefiltrate is evaporated and taken up in ether. The ethereal phase iswashed with 0.5N hydrochloric acid and then with a saturated aqueoussodium hydrogen carbonate solution. After decantation, it is dried overmagnesium sulphate and concentrated. The residue is purified on a silicacolumn (dichloromethane); the product is very volatile.

Colourless oil. m=4.1 g. Y=92%. ¹H NMR: 1.36-1.47 (2H, m), 1.58-1.70(2H, m), 2.02-2.11 (2H, m), 2.29-2.34 (2H, t), 3.67 (3H, s), 4.93-5.04(2H, m), 5.71-5.87 (1H, m).

b) Methyl7-(3-{2-[3,5-bis(Tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)hept-6-enoate.

In a manner similar to Example 1(h), by reacting 1.41 g (3.07 mmol) of3-bromo-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenylin 15 ml of dimethylformamide with the solution, at 0° C., of 8 ml (4mmol) of 9-borabicyclo[3.3.1]nonane 0.5M/THF and 567 mg (4 mmol) ofmethyl hept-6-enoate in 6 ml of THF, after purification on a silicacolumn (ethyl acetate 10-heptane 90), a yellow oil (m=971 mg; Y=61%) isobtained.

¹H NMR (CDCl₃): 1.46-1.93 (20H, m), 3.67 (3H, s), 3.61-3.67 (2H, m),3.89-3.98 (2H, m), 5.45-5.46 (2H, d), 6.18-6.43 (2H, m), 6.70 (1H, s),6.87-6.89 (2H, t), 6.97-7.04 (2H, m), 7.20-7.34 (3H, m), 7.45 (1H, s).

c)8-(3-{2-[3,5-bis(Tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)-2-methyloct-7-en-2-ol.

In a manner similar to Example 1(i), by reacting 2.2 ml (6.6 mmol) ofmethylmagnresium bromide 3M/ether with 859 mg (1.65 mmol) of7-(3-{2-[3,5-bis-(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)hept-6-enoatein 10 ml of ether, after purification on a silica column (ethyl acetate20-heptane 80), a yellow oil (m=306 mg; Y=36%) is obtained.

¹H NMR (CDCl₃): 1.22 (6H, s), 1.46-1.87 (20H, m), 3.61-3.67 (2H, m),3.89-3.98 (2H, m), 5.45-5.46 (2H, m), 6.20-6.43 (2H, m), 6.70 (1H, s),6.87-6.88 (2H, m), 7.04-7.06 (2H, m), 7.21-7.34 (3H, m), 7.45 (1H, s).

d) 5-{2-[3-(7-Hydroxy-7-methyloct-1-enyl)phenyl]-vinyl}benzene-1,3-diol.

In a manner similar to Example 25(d), by reacting 0.037 ml ofconcentrated sulphuric acid with 374 mg (0.72 mmol) of8-(3-{2-[3,5-bis(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)-2-methyloct-7-en-2-olin 4 ml of THF and 2 ml of water, after purification on a silica column(ethyl acetate 40-heptane 60), a beige powder (m=40 mg; Y=16%) isobtained. m.p.=152-4° C.

¹H NMR (CDCl₃): 1.21 (6H, s), 1.48 (6H, m), 2.24-2.26 (2H, m), 2.36 (1H,OH, s), 6.23-6.42 (3H, m), 6.53-6.54 (2H, d), 6.97 (2H, d), 7.23-7.29(3H, m), 7.42 (1H, s), 8.57 (2H, OH, s).

EXAMPLE 325-{2-[3-(7-Hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol

a) Methyl7-(3-{2-[3,5-bis-(Tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)heptanoate.

In a manner similar to Example 1(h), by reacting 1.51 g (3.28 mmol) of3-bromo-{2-[3-(tetrahydropyran-2-yl)-5-(tetrahydropyran-2-yloxy)phenyl]-vinyl}phenylin 15 ml of dimethylformamide with the solution at 0° C., 9.85 ml (4.92mmol) of 9-borabicyclo[3.3.1]nonane 0.5 M/THF and 520 mg (3.61 mmol) ofmethyl hept-6-enoate in 5 ml of THF, after purification on a silicacolumn (ethyl acetate 20-heptane 80), a yellow oil (m=1.75 g; Y=100%) isobtained.

¹H NMR (CDCl₃): 1.34-1.92 (22H, m), 2.57-2.64 (2H, t), 3.66 (3H, s),3.61-3.66 (2H, m), 3.89-3.98 (2H, m), 5.45-5.46 (2H, d), 6.69-6.70 (1H,d), 6.87-6.88 (2H, t), 7.03-7.10 (3H, m), 7.21-7.35 (3H, m).

b)8-(3-{2-(3,5-bis(Tetrahydropyran-2-yloxy)phenyl]-vinyl}phenyl)-2-methyloctan-2-ol.

In a manner similar to Example 1(i), by reacting 4.45 ml (13.3 mmol) ofmethylmagnesium bromide 3M/ether with 1.73 g (3.31 mmol) of methyl7-(3-{2-[3,5-bis(tetrahydropyran-2-yloxy)phenyl]-vinyl}phenyl)heptanoatein 20 ml of ether, after purification on a silica column (ethyl acetate20-heptane 80), a yellow oil (m=1.2 g; Y=69%) is obtained.

¹H NMR (CDCl₃): 1.20 (6H, s), 1.28-1.87 (22H, m), 2.57-2.60 (2H, t),3.65 (2H, m), 3.93 (2H, m), 5.46 (2H, m), 6.50-6.78 (2H, m), 6.88 (1H,s), 6.98-7.08 (3H, m), 7.25-7.29 (3H, m).

c) 5-{2-[3-(7-Hydroxy-7-methyloctyl)phenyl]vinyl}-benzene-1,3-diol.

In a manner similar to Example 25(d), by reacting 0.06 ml ofconcentrated sulphuric acid with 1.15 g (2.21 mmol) of8-(3-{2-[3,5-bis(tetrahydropyran-2-yloxy)phenyl]vinyl}phenyl)-2-methyloctan-2-olin 20 ml of THF and 10 ml of water, after purification on a silicacolumn (ethyl acetate 40-heptane 60), pinkish crystals (m=331 mg; Y=42%)are obtained.

m.p.=127-8° C. ¹H NMR (CDCl₃): 1.16 (6H, s), 1.40 (8H, m), 1.70 (2H, m),2.66-2.69 (2H, t), 4.16 (1H, OH, s), 6.27 (1H, s), 6.55 (2H, s),7.13-7.20 (3H, m), 7.33-7.39 (1H, t), 7.47-7.51 (2H, m), 9.37 (2H, OH,s).

EXAMPLE 334-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,2-diol

a) 3,4-bis(tert-Butyldimethylsilanyloxy)benzaldehyde.

In a manner similar to Example 3(c), by reacting 68.36 g (0.44 mol) oftributyldimethylsilane chloride with 27.62 g (0.2 mol) of3,4-dihydroxybenzaldehyde, 1.23 g of dimethylaminopyridine in 61.5 ml(0.44 mmol) of triethylamine and 900 ml of dimethylformamide, afterpurification on a silica column (ethyl acetate 5-heptane 95), anorange-coloured oil (m=69.82 g; Y=95%) is obtained.

¹H NMR (CDCl₃): 0.01 (6H, s), 0.02 (6H, s), 0.79 (18H, s), 6.72-6.75(1H, dd, J=5 Hz, J′=1.9 Hz), 7.14-7.18 (2H, m), 9.60 (1H, s).

b) 3-Bromo-[2-{3,4-bis-(tert-butyldimethylsilanyloxy)phenyl}vinyl]phenyl

In a manner similar to Example 1(g), by reacting 543 mg (18 mmol) ofsodium hydride with 5.5 g (15 mmol) of3,4-bis(tert-butyldimethylsilanyloxy)benzaldehyde and 5.53 g (18 mmol)of ethyl (3-bromobenzyl)phosphonate in 120 ml of THF, after purificationon a silica column (dichloromethane 10-heptane 90), a colourless oil(m=5.38 g; Y=69%) is obtained.

¹H NMR (CDCl₃): 0.20 (6H, s), 0.21 (6H, s), 0.99 (9H, s), 1.01 (9H, s),6.76-6.83 (2H, m), 6.94-7.00 (3H, m), 7.15-7.25 (1H, m), 7.32-7.39 (2H,m), 7.61-7.62 (1H, m).

c)2-[6-(3-{2-[3,4-bis(tert-Butyldimethylsilanyloxy)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]-tetrahydropyran.

In a manner similar to Example 8(j), by reacting 1.73 g (3.32 mmol) of3-bromo-[2-{3,4-bis(tert-butyldimethylsilanyloxy)phenyl}vinyl]phenyl in4 ml of ether with the solution of 222 mg (9.13 mmol) of magnesium, 2.43g (8.3 mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 8 mlof THF and catalysed by 72 mg (0.14 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a colourless oil (m=1.4 g;Y=65%) is obtained.

¹H NMR (CDCl₃): 0.21 (6H, s), 0.23 (6H, s), 0.99 (9H, s), 1.01 (9H, s),1.18-1.20 (6H, d), 1.26-1.83 (14H, m), 2.58-2.64 (2H, t), 3.38-3.47 (1H,m), 3.92-3.98 (1H, m), 4.69-4.71 (1H, m), 6.78-7.06 (6H, m), 7.20-7.32(3H, m).

d) 4-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}-benzene-1,2-diol.

In a manner similar to Example 25(d), by reacting 0.118 ml ofconcentrated sulphuric acid with 1.38 g (2.11 mmol) of2-[6-(3-{2-[3,4-bis(tert-butyldimethylsilanyloxy)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyranin 20 ml of THF and 10 ml of water, after purification on a silicacolumn (ethyl acetate 45-heptane 55), a solid having a cottonyappearance (m=522 mg; Y=77%) is obtained.

m.p.=138-9° C. ¹H NMR (CDCl₃): 1.20 (6H, s), 1.37-1.44 (6H, m),1.62-1.68 (2H, m), 2.58-2.64 (2H, t), 6.82-6.95 (4H, m), 7.01-7.08 (2H,m), 7.19-7.30 (3H, m), 7.58 (1H, OH, s), 7.69 (1H, OH, s).

EXAMPLE 34 3-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}phenol

a) 3-(tert-Butyldimethylsilanyloxy)benzaldehyde.

In a manner similar to Example 3(c), by reacting 42.72 g (0.275 mol) oftert-butyldimethylsilane chloride with 30.53 g (0.2 mol) of3-hydroxybenzaldehyde, 1.52 g of dimethylaminopyridine in 38.5 ml (0.275mmol) of triethylamine and 300 ml of dimethylformamide, afterpurification on a silica column (dichloromethane 20-heptane 80), ayellow oil (m=55.86 g; Y=95%) is obtained.

¹H NMR (CDCl₃): 0.20 (6H, s), 0.98 (9H, s) 7.06-7.10 (1H, m), 7.24-7.48(3H, m), 9.93 (1H, s).

b) {3-[2-(3-Bromophenyl)vinyl]phenoxy}-tert-butyldimethylsilane.

In a manner similar to Example 1(g), by reacting 543 mg (18 mmol) ofsodium hydride with 3.55 g (15 mmol) of3-(tert-butyldimethylsilanyloxy)benzaldehyde and 5.53 g (18 mmol) ofethyl (3-bromobenzyl)phosphonate in 100 ml of THF, after purification ona silica column (dichloromethane 10-heptane 90), a colourless oil(m=3.73 g; Y=64%) is obtained.

¹H NMR (CDCl₃): 0.22 (6H, s), 1.00 (9H, s), 6.74-6.78 (1H, dd, J=4.7 Hz,J′=1.5 Hz), 6.92-7.01 (3H, m), 7.08-7.25 (3H, m), 7.35-7.42 (2H, t),7.65-7.66 (1H, t).

c)tert-Butyldimethyl-[3-(2-{3-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]phenyl}vinyl)phenoxy]silane.

In a manner similar to Example 8(j), by reacting 1.30 g (3.32 mmol) of{3-[2-(3-bromophenyl)vinyl]phenoxy}-tert-butyldimethylsilane in 4 ml ofether with the solution of 222 mg (9.13 mmol) of magnesium, 2.43 g (8.3mmol) of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 8 ml of THFand catalysed by 72 mg (0.14 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a colourless oil (m=1.28g; Y=74%) is obtained.

¹H NMR (CDCl₃): 0.22 (6H, s), 1.00 (9H, s), 1.18-1.20 (6H, d), 1.25-1.83(14H, m), 2.59-2.65 (2H, t), 3.38-3.47 (1H, m), 3.92-3.98 (1H, m),4.69-4.71 (1H, m), 6.71-6.76 (1H, dd), 6.97-6.99 (1H, t), 7.06-7.34 (6H,m).

d) 3-{2-[3-(6-Hydroxy-6-methylheptyl)phenyl]vinyl}-phenol.

In a manner similar to Example 25(d), by reacting 0.133 ml ofconcentrated sulphuric acid with 1.25 g (2.39 mmol) oftert-butyldimethyl-[3-(2-{3-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]phenyl}-vinyl)phenoxy]silanein 20 ml of THF and 10 ml of water, after crystallization from aheptane/ethyl acetate mixture, white crystals (m=697 mg; Y=90%) areobtained. m.p.=96-7° C.

¹H NMR (CDCl₃): 1.22 (6H, s), 1.31-1.45 (6H, m), 1.60-1.70 (2H, m),2.59-2.65 (2H, t), 5.46 (1H, OH, s), 6.71-6.75 (1H, dd, J=6.2 Hz, J′=1.7Hz), 6.99-7.08 (5H, m), 7.18-7.33 (4H, m).

EXAMPLE 356-{3-[2-(3,5-bis-Hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol

a) 5-Bromoisophthalic Acid.

33.23 g (0.2 mol) of isophthalic acid and 37.42 g (0.12 mol) of silversulphate are dissolved in 330 ml of sulphuric acid. 13.3 ml (0.26 mol)of bromine are then added over 1 h. The solution is heated at 55° C. for24 h. The medium is then poured into ice, the insoluble material isfiltered and taken up in ethyl acetate. The remaining solid is taken upin water and basified with a saturated aqueous sodium hydrogen carbonatesolution. The insoluble material is filtered and the filtrate isacidified and then extracted with ethyl acetate. The organic phase iswashed with water and then dried over magnesium sulphate andconcentrated.

White powder. m=42.1 g. Y=86%. m.p.=285-7° C. ¹H NMR (DMSO): 8.40 (2H,s), 8.57 (1H, t), 13.76 (2H, COOH, s).

b) (3-Bromo-5-hydroxymethylphenyl)methanol.

In a manner similar to Example 1(c), by reacting 690 ml of boran 1M/THFwith 42.06 g (0.172 mol) of 5-bromoisophthalic acid in 420 ml of THF,after trituration in heptane, a white powder (m=28.19 g; Y=76%) isobtained. m.p.=85-8° C.

¹H NMR (DMSO): 4.65 (4H, s), 5.48 (2H, OH, s), 7.41 (1H, s), 7.52 (2H,s).

c) 1-Bromo-3,5-bis-(tert-butyldimethylsilanyloxymethyl)benzene.

In a manner similar to Example 3(c), by reacting 44.43 g (0.286 mol) oftert-butyldimethylsilane chloride with 28.18 g (0.13 mol) of(3-bromo-5-hydroxymethylphenyl)methanol, 794 mg of dimethylaminopyridinein 40 ml of (0.286 mmol) of triethylamine and 700 ml ofdimethylformamide, after purification on a silica column(dichloromethane 10-heptane 90), a yellowish oil (m=50.84 g; Y=98%) isobtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 4.59 (4H, s), 7.10 (1H,s), 7.22 (2H, s).

d) 3,5-bis-(tert-Butyldimethylsilanyloxymethyl)benzaldehyde.

In a manner similar to Example 4(c), by reacting 13.5 ml (33.75 mmol) ofn-butyllithium 2.5M/hexane, at −78° C., with 13.4 g (30 mmol) of1-bromo-3,5-bis-(tert-butyldimethylsilanyloxymethyl)benzene in 140 ml ofTHF and 30 minutes later, with 2.55 ml (33 mmol) of dimethylformamide,after purification on a silica column (dichloromethane 60-heptane 40), ayellowish oil (m=9.5 g; Y=80%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 4.68 (4H, s), 7.48 (1H,s), 7.58 (2H, s), 9.89 (1H, s).

e)3-Bromo-[2-{3,5-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl.

In a manner similar to Example 1(g), by reacting 362 mg (12 mmol) ofsodium hydride with 3.95 g (10 mmol) of3,5-bis-(tert-butyldimethylsilanyloxymethyl)benzaldehyde and 3.61 g (12mmol) of ethyl (3-bromobenzyl)phosphonate in 80 ml of THF, afterpurification on a silica column (dichloromethane 10-heptane 90), ayellowish oil (m=4.93 g; Y=90%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 4.63 (4H, s), 6.84-7.01(2H, q), 7.05-7.12 (2H, m), 7.21-7.30 (4H, m), 7.52-7.53 (1H, t).

f) Methyl5-(3-{2-[3,5-bis-(tert-Butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)pentanoate.

In a manner similar to Example 1(h), by reacting 1.64 g (3 mmol) of3-bromo-[2-{3,5-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenylin 20 ml of dimethylformamide with the solution, at 0° C., of 9 ml (4.5mmol) of 9-borabicyclo[3.3.1]nonane 0.5 M/THF and 397 mg (3.3 mmol) ofmethyl pent-4-enoate in 5 ml of THF, after purification on a silicacolumn (dichloromethane 40-heptane 80), a yellowish oil (m=1.14 g;Y=65%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 1.37-1.77 (6H, m),2.50-2.55 (2H, t), 3.54 (3H, s), 4.63 (4H, s), 6.93-6.96 (3H, m),7.08-7.22 (6H, m).

g)6-(3-{2-[3,5-bis-(tert-Butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-2-methylhexan-2-ol.

In a manner similar to Example 1(i), by reacting 2.6 ml (7.73 mmol) ofmethylmagnesium bromide 3M/ether with 1.13 g (1.93 mmol) of methyl5-(3-{2-[3,5-bis(tert-butyldimethylsilanyloxymethyl)phenyl]-vinyl}phenyl)pentanoatein 10 ml of ether, after purification on a silica column (ethyl acetate15-heptane 85), a yellow oil (m=886 mg; Y=79%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 1.09 (6H, s), 1.14-1.60(6H, m), 2.50-2.56 (2H, t), 4.63 (4H, s), 6.94-6.96 (3H, m), 7.08-7.22(6H, m).

h)6-{3-[2-(3,5-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylhexan-2-ol.

In a manner similar to Example 3(i), by reacting 858 mg (1.47 mmol) of6-(3-{2-[3,5-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-2-methylhexan-2-olwith 3.25 ml of tetrabutylammonium fluoride 1M/THF, after purificationon a silica column (ethyl acetate), a white paste (m=460 mg; Y=88%) isobtained.

¹H NMR (CDCl₃): 1.20 (6H, s), 1.37-1.71 (6H, m), 2.61-2.67 (2H, t), 4.69(4H, s), 7.03-7.17 (3H, m), 7.23-7.34 (4H, m), 7.42 (2H, s).

EXAMPLE 36 3-{2-[3-(7-Hydroxy-7-methyloctyl)phenyl]vinyl}phenol

a) Methyl7-(3-{2-[tert-Butyldimethylsilanyloxy)phenyl]vinyl}phenyl)heptanoate.

In a manner similar to Example 1(h), by reacting 1.17 g (3 mmol) of{3-[2-(3-bromophenyl)vinyl]phenoxy}-tert-butyldimethylsilane in 12 ml ofdimethylformamide with the solution at 0° C., of 9 ml (4.5 mmol) of9-borabicyclo[3.3.1]nonane 0.5 M/THF and 470 mg (3.3 mmol) of methylhex-5-enoate in 5 ml of THF, after purification on a silica column(dichloromethane 40-heptane 80), a yellowish oil (m=270 mg; Y=20%) isobtained.

¹H NMR (CDCl₃): 0.22 (6H, s), 1.00 (9H, s), 1.33-1.39 (4H, m), 1.55-1.63(4H, m), 2.27-2.33 (2H, t), 2.58-2.64 (2H, t), 3.66 (3H, s), 6.72-6.76(1H, m), 6.97-6.99 (1H, t), 7.08-7.34 (8H, m).

b)8-(3-{2-[3-(tert-Butyldimethylsilanyloxy)phenyl]-vinyl}phenyl)-2-methyloctan-2-ol.

In a manner similar to Example 1(i), by reacting 0.77 ml (2.29 mmol) ofmethylmagnesium bromide 3M/ether with 259 mg (0.57 mmol) of methyl7-(3-{2-[tert-butyldimethylsilanyloxy)phenyl]vinyl}phenyl)heptanoate in3 ml of ether, after purification on a silica column (ethyl acetate20-heptane 80), a yellowish paste (m=219 mg; Y=81%) is obtained.

¹H NMR (CDCl₃): 0.21 (6H, s), 1.00 (9H, s), 1.20 (6H, s), 1.28-1.43 (8H,m), 1.61-1.65 (2H, m), 2.59-2.65 (2H, t), 6.72-6.76 (1H, m), 6.97-6.99(1H, t), 7.06-7.35 (8H, m)

c) 3-{2-[3-(7-Hydroxy-7-methyloctyl)phenyl]vinyl}-phenol.

In a manner similar to Example 3(i), by reacting 207 mg (0.46 mmol) of8-(3-{2-[3-(tert-butyldimethylsilanyloxy)phenyl]vinyl}phenyl)-2-methyloctan-2-olwith 0.5 ml of tetrabutylammonium fluoride 1M/THF, after purification ona silica column (ethyl acetate 30-heptane 70), a white powder (m=203 mg;Y=32%) is obtained. m.p.=142-3° C.

¹H NMR (DMSO): 1.05 (6H, s), 1.30 (8H, m), 1.59 (2H, m), 2.55-2.61 (2H,t), 4.03 (1H, OH, s), 6.66-6.69 (1H, dd, J=6.3 Hz, J′=1.6 Hz), 6.96-7.28(7H, m), 7.36-7.39 (2H, d, J=7.7 Hz).

EXAMPLE 377-{3-[2-(3,5-bis-Hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol

a)2-[6-(3-{2-[3,5-bis-(tert-Butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]-tetrahydropyran.

In a manner similar to Example 8(j), by reacting 2.40 g (4.38 mmol) of3-bromo-[2-{3,5-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenylwith the solution of 293 mg (12 mmol) of magnesium, 3.12 g (10.6 mmol)of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 10 ml of THF andcatalysed by 94 mg (0.178 mmol) of[1,2-bis-(diphenylphosphino)ethane]-dichloronickel, after purificationon a silica column (ethyl acetate 3-heptane 97), a colourless oil(m=2.05 g; Y=69%) is obtained.

¹H NMR (CDCl₃): 0.00 (12H, s), 0.84 (18H, s), 1.06-1.08 (6H, d),1.13-1.71 (14H, m), 2.47-2.53 (2H, t), 3.29-3.33 (1H, m), 3.80-3.84 (1H,m), 4.57-4.59 (1H, m), 4.63 (4H, s), 6.94-6.97 (3H, m), 7.08-7.22 (6H,m).

b)7-{3-[2-(3,5-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 25(d), by reacting 0.5 ml of concentratedsulphuric acid with 2.04 g (3 mmol) of2-[6-(3-{2-[3,5-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyranin 30 ml of THF and 10 ml of water, after purification on a silicacolumn (ethyl acetate 80-heptane 20), white crystals (m=646 mg; Y=58%)are obtained. m.p.=108-9° C.

¹H NMR (CDCl₃): 1.18 (6H, s), 1.37-1.43 (6H, m), 1.63-1.68 (2H, m),2.59-2.65 (2H, t), 4.29-4.34 (2H, OH, t), 4.64 (2H, s), 4.67 (2H, s),7.06-7.11 (3H, m), 7.18-7.30 (4H, m), 7.42-7.43 (2H, d).

EXAMPLE 387-{3-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol

a)2-[6-(3-{2-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]-tetrahydropyran.

In a manner similar to Example 8(j), by reacting 2.40 g (4.38 mmol) of3-bromo-[2-{3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl}vinyl]phenylwith the solution of 293 mg (12 mmol) of magnesium, 3.12 g (10.6 mmol)of 2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 10 ml of THF andcatalysed by 94 mg (0.178 mmol) of[1,2-bis-(diphenylphosphino)ethane]dichloronickel, after purification ona silica column (ethyl acetate 3-heptane 97), a colourless oil (m=2.31g; Y=77%) is obtained.

¹H NMR (CDCl₃): −0.02 (6H, s), 0.00 (6H, s), 0.83 (9H, s), 0.84 (9H, s),1.06-1.08 (6H, d), 1.13-1.71 (14H, m), 2.47-2.53 (2H, t), 3.28-3.33 (1H,m), 3.80-3.84 (1H, m), 4.57 (1H, m), 4.62 (2H, s), 4.64 (2H, s),6.93-6.97 (3H, m), 7.10-7.27 (5H, m), 7.46 (1H, s).

b)7-{3-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 25(d), by reacting 0.56 ml ofconcentrated sulphuric acid with 2.30 g (3.37 mmol) of2-[6-(3-{2-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]vinyl}phenyl)-1,1-dimethylhexyloxy]tetrahydropyranin 30 ml of THF and 10 ml of water, after purification on a silicacolumn (ethyl acetate 80-heptane 20), white crystals (m=475 mg; Y=38%)are obtained. m.p.=93-5° C.

¹H NMR (CDCl₃): 1.19 (6H, s), 1.28-1.42 (6H, m), 1.62-1.68 (2H, m),2.59-2.65 (2H, t), 3.50 (2H, OH, s), 4.66 (2H, s), 4.70 (2H, s),7.00-7.14 (3H, m), 7.22-7.32 (4H, m), 7.39-7.44 (1H, dd, J=6.2 Hz,J′=1.55 Hz), 7.47 (1H, s).

EXAMPLE 397-{3-[2-(4-Hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol

a) (4-Bromobenzyloxy)-tert-butyldimethylsilane.

In a manner similar to Example 3(c), by reacting 54.3 g (0.36 mol) oftert-butyldimethylsilane chloride with 56.1 g (0.3 mol) of(4-bromophenyl)methanol, 8.8 g (72 mmol) of dimethylaminopyridine in 100ml of triethylamine and 150 ml of dimethylformamide, after purificationon a silica column (heptane), a greenish-yellow oil (m=81 g; Y=90%) isobtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.84 (9H, s), 4.58 (2H, s), 7.08-7.11 (2H,d, J=8.3 Hz), 7.33-7.37 (2H, d, J=8.4 Hz).

b) 4-(tert-Butyldimethylsilanyloxymethyl)benzaldehyde.

In a manner similar to Example 4(c), by reacting 13.2 [lacuna] ofn-butyllithium 2.5 M/hexane, at −78° C., with 9.04 g (30 mmol) of(4-bromobenzyloxy)tert-butyldimethylsilane in 90 ml of THF and 30minutes later, with 2.55 ml (33 mmol) of dimethylformamide, afterpurification on a silica column (ethyl acetate 5-heptane 60), ayellowish oil (m=3.64 g; Y=48%) is obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.83 (9H, s), 4.69 (2H, s), 7.35-7.38 (2H,d, J=8.07 Hz), 7.71-7.75 (2H, d, J=8.2 Hz).

c) {4-[2-(3-Bromophenyl)vinyl]benzyloxy}-tert-butyldimethylsilane.

In a manner similar to Example 1(g), by reacting 513 mg (17 mmol) ofsodium hydride with 3.64 g (14 mmol) of4-(tert-butyldimethylsilanyloxymethyl)benzaldehyde and 5.36 g (17 mmol)of ethyl (3-bromobenzyl)phosphonate in 90 ml of THF, after purificationon a silica column (dichloromethane 5-heptane 95), white crystals(m=4.61 g; Y=82%) are obtained.

m.p.=65-7° C. ¹H NMR (CDCl₃): 0.10 (6H, s), 0.93 (9H, s), 4.74 (2H, s),6.95-7.13 (2H, dd, J=11.9 Hz, J′=16.3 Hz), 7.17-7.25 (1H, m), 7.30-7.48(6H, m), 7.64-7.66 (1H, t).

d)tert-Butyldimethyl-[4-(2-{3-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]phenyl}vinyl)benzyloxy]-silane.

In a manner similar to Example 8(j), by reacting 1.77 g (4.38 mmol) of{4-[2-(3-bromophenyl)vinyl]benzyloxy}-tert-butyldimethylsilane with thesolution of 293 mg (12 mmol) of magnesium, 3.12 g (10.6 mmol) of2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 10 ml of THF andcatalysed by 94 mg (0.178 mmol) of[1,2-bis-(diphenylphosphino)ethane]-dichloronickel, after purificationon a silica column (ethyl acetate 3-heptane 97), a colourless oil (m=1g; Y=43%) is obtained.

¹H NMR (CDCl₃): 0.00 (6H, s), 0.84 (9H, s), 1.07-1.09 (6H, d), 1.24-1.53(14H, m), 2.48-2.54 (2H, t), 3.30-3.34 (1H, m), 3.81-3.85 (1H, m), 4.58(1H, m), 4.63 (2H, s), 6.94-6.97 (3H, m), 7.11-7.21 (5H, s), 7.35-7.38(2H, d, J=8.2 Hz).

e) 7-{3-[2-(4-Hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 25(d), by reacting 0.2 ml of concentratedsulphuric acid with 1 g (1.86 mmol) oftert-butyldimethyl-[4-(2-{3-[6-methyl-6-(tetrahydropyran-2-yloxy)heptyl]phenyl}vinyl)benzyloxy]silanein 20 ml of THF and 10 ml of water, after purification on a silicacolumn (ethyl acetate 50-heptane 50), white crystals (m=350 mg; Y=56%)are obtained. m.p.=105-7° C.

¹H NMR (CDCl₃): 1.19 (6H, s), 1.28-1.43 (6H, m), 1.63-1.69 (2H, m),2.59-2.65 (2H, t), 4.67 (2H, s), 7.06-7.09 (3H, m), 7.23-7.36 (5H, m),7.48-7.51 (2H, d, J=8.2 Hz).

EXAMPLE 404-{2-[3-(7-Hydroxy-7-methyloct-1-enyl)phenyl]vinyl}-benzene-1,2-diol

a) Methyl7-(3-{2-[3,4-bis-(tert-Butyldimethylsilanyloxy)phenyl]vinyl}phenyl)hept-6-enoate.

0.43 ml of triethylamine and 72 mg (0.077 mmol) of[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium are added to asolution of 1.33 g (2.56 mmol) of3-bromo-[2-{3,4-bis-(tert-butyldimethylsilanyloxy)phenyl}vinyl]phenyland 444 mg (3.1 mmol) of methyl hept-6-enoate in 20 ml ofdimethylformamide. The medium is heated at 75° C. for 3 days. It is thenpoured into a saturated aqueous ammonium chloride solution and extractedwith ether. The organic phase is washed with a saturated aqueous sodiumchloride solution and then with water. After decantation, it is driedover magnesium sulphate and concentrated. The residue is purified on asilica column (ethyl acetate 5-heptane 95).

Yellow oil. m=318 mg. Y=21%. ¹H NMR (CDCl₃): 0.21 (6H, s), 0.23 (6H, s),1.00 (9H, s), 1.03 (9H, s), 1.48-1.55 (2H, m), 1.64-1.78 (2H, m),2.21-2.29 (2H, m), 2.32-2.41 (2H, t), 3.67 (3H, s), 6.18-6.30 (1H, m),6.37-6.44 (1H, d, J=15.9 Hz), 6.79-7.02 (6H, m), 7.14-7.43 (2H, m), 7.62(1H, s).

b)8-(3-{2-[3,4-bis-(tert-Butyldimethylsilanyloxy)phenyl]vinyl}phenyl)-2-methyloct-7-en-2-ol.

In a manner similar to Example 1(i), by reacting 1 ml (3 mmol) ofmethylmagnesium bromide 3M/ether with 305 mg (0.52 mmol) of methyl7-(3-{2-[3,4-bis-(tert-butyldimethylsilanyloxy)phenyl]-vinyl}phenyl)hept-6-enoatein 6 ml of ether, after purification on a silica column (ethyl acetate20-heptane 80), a yellow oil (m=190 mg; Y=63%) is obtained.

¹H NMR (CDCl₃): 0.21 (6H, s), 0.23 (6H, s), 0.99 (9H, s), 1.01 (9H, s),1.23 (6H, s), 1.38-1.62 (6H, m), 2.24-2.26 (2H, m), 6.20-6.32 (1H, m),6.37-6.44 (1H, d, J=15.9 Hz), 6.79-7.02 (5H, s), 7.20-7.34 (3H, m), 7.44(1H, s).

c) 4-{2-[3-(7-Hydroxy-7-methyloct-1-enyl)phenyl]-vinyl}benzene-1,2-diol.

In a manner similar to Example 3(i), by reacting 166 mg (0.286 mmol) of8-(3-{2-[3,4-bis-(tert-butyldimethylsilanyloxy)phenyl]vinyl}phenyl)-2-methyloct-7-en-2-olwith 0.63 ml of tetrabutylammonium fluoride 1M/THF, after purificationon a silica column (ethyl acetate 45-heptane 55), white crystals (m=65mg; Y=64%) are obtained. m.p.=116-8° C.

¹H NMR (CDCl₃): 1.21 (6H, s), 1.47-1.54 (6H, m), 2.23-2.25 (2H, m),6.19-6.31 (1H, m), 6.36-6.42 (1H, d, J=15.9 Hz), 6.82-7.33 (8H, m), 7.41(1H, s).

EXAMPLE 417-[3-(3,4-bis-Hydroxymethylphenylethynyl)phenyl]-2-methylheptan-2-ol

a) 1,2-bis-(tert-Butyldimethylsilanyloxymethyl)-4-ethynylbenzene.

7.5 ml (18.4 mmol) of n-butyllithium 2.5M/hexane are added, at −78° C.,to 2.62 ml (18.4 mmol) of diisopropylamine in 50 ml of THF. The solutionis stirred for 1 hour and then, still at −78° C., 9.2 ml (18.4 mmol) of(trimethylsilyl)diazomethane 2M/hexane are added dropwise. After 40 min,3.64 g (9.2 mmol) of4-(tert-butyldimethylsilanyloxy)-3-(tert-butyldimethylsilanyloxymethyl)benzaldehydein 40 ml of THF are added. The medium is further stirred for 1 hour at−78° C. and then it is allowed to return to room temperature over 12hours. It is then poured into a saturated aqueous ammonium chloridesolution and extracted with ether. The organic phase is washed withwater, dried over magnesium sulphate and then concentrated. The residueis purified on a silica column (dichloromethane 20-heptane 80).

Yellowish oil. m=952 mg. Y=26%. ¹H NMR (CDCl₃): 0.00 (6H, s), 0.01 (6H,s), 0.83 (18H, s), 2.94 (1H, s), 4.59 (2H, s), 4.63 (2H, s), 7.29-7.30(2H, d), 7.44 (1H, s).

b)3-Bromo-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenylethynyl]phenyl.

949 mg (2.42 mmol) of1,2-bis-(tert-butyldimethylsilanyloxymethyl)-4-ethynylbenzene and 707 mg(2.42 mmol) of 3-iodo-1-bromobenzene are dissolved in 20 ml oftriethylamine. The solution is degassed with nitrogen for 1 hour 30minutes and then 136 mg (0.19 mmol) of PdCl₂(PPh₃)₂ and 56 mg (0.29mmol) of copper iodide are added. The mixture is kept stirring for 12hours at room temperature. The triethylamine is then evaporated and theresidue is purified on a silica column (dichloromethane 20-heptane 80).

Yellow oil. m=1.27 g. Y=96%. ¹H NMR (CDCl₃): 0.00 (6H, s), 0.01 (6H, s),0.84 (18H, s), 4.61 (2H, s), 4.65 (2H, s), 7.07-7.14 (1H, t), 7.33-7.37(4H, m), 7.45 (1H, s), 7.57-7.58 (1H, t).

c) Methyl6-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenylethynyl]phenyl}hexanoate.

In a manner similar to Example 1(h), by reacting 663 mg (1.21 mmol) of3-bromo-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenylethynyl]phenylin 12 ml of dimethylformamide with the solution at 0° C., 985 mg (4.04mmol) of 9-borabicyclo[3.3.1]nonane in 10 ml of THF and 259 mg (2.02mmol) of methyl hex-5-enoate in 5 ml of THF, after purification on asilica column (ethyl acetate 5-heptane 95), a yellow oil (m=326 mg;Y=45%) is obtained.

¹H NMR (CDCl₃): −0.01 (6H, s), 0.00 (6H, s), 0.83 (18H, s), 1.21-1.81(6H, m), 2.17-2.23 (2H, t), 2.46-2.52 (2H, t), 3.55 (3H, s), 4.61 (2H,s), 4.65 (2H, s), 7.00-7.03 (1H, d), 7.10-7.17 (1H, t), 7.23-7.24 (2H,t), 7.31-7.32 (2H, d), 7.44 (1H, s).

d)7-{3-[3,4-bis-(tert-Butyldimethylsilanyloxymethyl)phenylethynyl]phenyl}-2-methylheptan-2-ol.

In a manner similar to Example 1(i), by reacting 0.7 ml (2.11 mmol) ofmethylmagnesium bromide 3M/ether with 314 mg (0.53 mmol) of6-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenylethynyl]-phenyl}hexanoatein 6 ml of ether, after purification on a silica column (ethyl acetate10-heptane 90), a yellow oil (m=252 mg; Y=80%) is obtained.

¹H NMR (CDCl₃): −0.01 (6H, s), 0.00 (6H, s), 0.83 (18H, s), 1.14-1.66(8H, m), 2.46-2.53 (2H, t), 4.61 (2H, s), 4.65 (2H, s), 7.01-7.04 (1H,d), 7.11-7.17 (1H, m), 7.23-7.25 (2H, d), 7.31-7.32 (2H, d), 7.44 (1H,s).

e) 7-[3-(3,4-bis-Hydroxymethylphenylethynyl)phenyl]-2-methylheptan-2-ol.

In a manner similar to Example 3(i), by reacting 250 mg (0.42 mmol) of7-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenylethynyl]phenyl}-2-methylheptan-2-olwith 0.93 ml of tetrabutylammonium fluoride 1M/THF, after purificationon a silica column (ethyl acetate 70-heptane 30), white crystals (m=132mg; Y=86%) are obtained. m.p.=52-5° C.

¹H NMR (CDCl₃): 1.19 (6H, s), 1.37-1.64 (8H, m), 2.57-2.63 (2H, t), 3.18(2H, OH, s), 4.71 (4H, s), 7.13-7.16 (1H, d, J=7.4 Hz), 7.22-7.35 (4H,m), 7.45-7.51 (2H, m).

EXAMPLE 425-{2-[3-(6-Hydroxy-6-methylhept-1-enyl)phenyl]vinyl}-benzene-1,3-diol

a) Methyl 3,5-bis-Ethoxymethoxybenzoate.

In a manner similar to Example 1(d), by reacting 42.04 g (0.25 mol) ofmethyl 3,5-dihydroxybenzoate in 400 ml of dimethylformamide with 18.09 g(0.6 mol) of sodium hydride and 51.26 g (0.515 mol) of methoxymethylchloride, after purification on a silica column (dichloromethane), ayellow oil (m=37.72 g; Y=62%) is obtained.

¹H NMR (CDCl₃): 1.19-1.25 (6H, t), 3.68-3.77 (4H, q), 3.89 (3H, s), 5.23(4H, s), 6.92-6.94 (1H, t), 7.35-7.36 (2H, d).

b) (3,5-bis-Ethoxymethoxyphenyl)methanol.

In a manner similar to Example 1(e), by reacting 400 ml ofdiisobutylaluminium hydride 1M/toluene, at −78° C., with 37.7 g (0.133mol) of methyl 3,5-bis-ethoxymethoxybenzoate, after purification on asilica column (ethyl acetate 20-heptane 80), a yellow oil (m=38.1 g;Y=86%) is obtained.

¹H NMR (CDCl₃): 1.19-1.24 (6H, t), 3.67-3.76 (4H, q), 4.61 (2H, s), 5.19(4H, s), 6.64-6.66 (1H, t), 6.69-6.70 (2H, d).

c) 3,5-bis-Ethoxymethoxybenzaldehyde.

97 g (1.11 mol) of manganese dioxide are added to a solution of 40.78 g(0.159 mol) of (3,5-bis-ethoxymethoxyphenyl)methanol in 400 ml ofdichloromethane. The medium is stirred at room temperature for 5 days.It is then filtered on silica and the solid is washed withdichloromethane. The filtrate is evaporated.

Yellow oil. m=36.51 g. Y=90%. ¹H NMR (CDCl₃): 1.20-1.25 (6H, t)3.69-3.78 (4H, q), 5.25 (4H, s), 6.98-6.99 (1H, t), 7.20-7.21 (2H, d).

d) 3-Bromo-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl.

In-a manner similar to Example 1(g), by reacting 2.05 g (68 mmol) ofsodium hydride with 14.5 g (57 mmol) of3,5-bis-ethoxymethoxybenzaldehyde and 20.88 g (68 mmol) of ethyl3-bromobenzylphosphonate in 350 ml of THF, after purification on asilica column (dichloromethane 30-heptane 70), a yellow oil (m=22.83 g;Y=98%) is obtained.

¹H NMR (CDCl₃): 1.21-1.27 (6H, t), 3.70-3.79 (4H, q), 5.23 (4H, s),6.68-6.69 (1H, t), 6.85-6.86 (2H, d), 6.93-7.07 (2H, dd, J=16.3 Hz,J′=2.55 Hz), 7.17-7.24 (1H, t), 7.35-7.41 (2H, t), 7.64-7.65 (1H, t).

e) Methyl6-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]phenyl}-hex-5-enoate.

In a manner similar to Example 40(a), by reacting 4.07 g (0.01 mol) of3-bromo-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl in 50 ml oftriethylamine with 1.54 g (0.012 mol) of methyl hex-5-enoate and ascatalyst 112 mg (0.5 mmol) of palladium acetate and 262 mg (1 mmol) oftriphenylphosphine, after purification on a silica column (ethyl acetate10-heptane 90), a yellow oil (m=2 g; Y=44%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 1.78-1.89 (2H, m), 2.23-2.41 (4H, m),3.67 (3H, s), 3.63-3.79 (4H, m), 5.24 (4H, s), 6.17-6.28 (1H, m),6.38-6.45 (1H, d, J=15.9 Hz), 6.67 (1H, s), 6.87 (2H, d), 7.05-7.07 (2H,d), 7.22-7.36 (3H, m), 7.47 (1H, s).

f)7-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-2-methylhept-6-en-2-ol.

In a manner similar to Example 1(i), by reacting 6.9 ml (21 mmol) ofmethylmagnesium bromide 3M/ether with 935 mg (2.06 mmol) of methyl6-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}hex-5-enoate in 20 mlof ether, after purification on a silica column (ethyl acetate30-heptane 70), a yellow oil (m=352 mg; Y=36%) is obtained.

¹H NMR (CDCl₃): 1.23 (6H, s), 1.18-1.28 (6H, m), 1.51-1.69 (4H, m),2.21-2.26 (2H, m), 3.71-3.79 (4H, q), 5.24 (4H, s), 6.21-6.33 (1H, m),6.38-6.44 (1H, d, J=15.9 Hz), 6.66-6.67 (1H, t), 6.87-6.88 (2H, d),7.04-7.05 (2H, d), 7.22-7.36 (3H, m), 7.47 (1H, s).

g)5-{2-[3-(6-Hydroxy-6-methylhept-1-enyl)phenyl]-vinyl}benzene-1,3-diol.

In a manner similar to Example 1(j), by reacting 0.15 ml of concentratedsulphuric acid in 3 ml of methanol with 314 mg (0.67 mmol) of7-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-2-methylhept-6-en-2-olin 3 ml of methanol and 3 ml of THF, after purification on a silicacolumn (ethyl acetate 50-heptane 50), white crystals (m=206 mg; Y=91%)are obtained. m.p.=60-4° C.

¹H NMR (CDCl₃): 1.24 (6H, s), 1.53-1.61 (4H, m), 2.17-2.22 (2H, m),6.18-6.30 (1H, m), 6.35-6.36 (2H, d), 6.57 (2H, d), 6.89-7.03 (2H, m),7.21-7.30 (3H, m), 7.40 (1H, s), 7.96 (2H, OH, s).

EXAMPLE 435-{2-[3-(7-Ethyl-7-hydroxynon-1-enyl)phenyl]vinyl}-benzene-1,3-diol

a) Methyl7-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]phenyl}hept-6-enoate.

In a manner similar to Example 40(a), by reacting 1.03 g (2.5 mmol) of3-bromo-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl in 30 ml ofdimethylformamide with 430 mg (3 mmol) of methyl hept-6-enoate and 700mg (5 mmol) of potassium carbonate and as catalyst 82 mg (0.1 mmol) of[1,1′-bis-(diphenylphosphino)ferrocene]dichloropalladium, afterpurification on a silica column (ethyl acetate 10-heptane 90), ayellowish oil (m=843 mg; Y=72%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 1.47-1.85 (4H, m), 2.21-2.42 (4H, m),3.66 (3H, s), 3.67-3.79 (4H, q), 5.24 (4H, s), 6.19-6.30 (1H, m),6.37-6.44 (1H, d, J=15.9 Hz), 6.66-6.67 (1H, t), 6.87 (2H, d), 7.05-7.07(2H, m), 7.21-7.41 (3H, m), 7.47 (1H, s).

b)9-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-3-ethylnon-8-en-3-ol.

In a manner similar to Example 1(i), by reacting 7 ml of ethylmagnesiumbromide 1M/THF with 824 mg (1.76 mmol) of methyl7-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}hept-6-enoate in 20 mlof ether, after purification on a silica column (ethyl acetate15-heptane 85), a yellow oil (m=728 mg; Y=83%) is obtained.

¹H NMR (CDCl₃): 0.81-0.89 (6H, m), 1.22-1.27 (6H, m), 1.34-1.51 (10H,m), 2.17-2.29 (2H, m), 3.71-3.79 (4H, q), 5.24 (4H, s), 6.21-6.32 (1H,m), 6.37-6.43 (1H, d, J=15.9 Hz), 6.66-6.67 (1H, t), 6.87 (2H, d),7.05-7.07 (2H, m), 7.22-7.36 (3H, m), 7.47 (1H, s).

c) 5-{2-[3-(7-Ethyl-7-hydroxynon-1-enyl)phenyl]-vinyl}benzene-1,3-diol.

In a manner similar to Example 1(j), by reacting 0.3 ml of concentratedsulphuric acid in 7 ml of methanol with 700 mg (1.41 mmol) of9-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-3-ethylnon-8-en-3-olin 7 ml of methanol and 7 ml of THF, after purification on a silicacolumn (ethyl acetate 40-heptane 60), beige crystals (m=477 mg; Y=77%)are obtained. m.p.=98-102° C.

¹H NMR (CDCl₃): 0.67-0.73 (6H, m), 1.25-1.31 (8H, m), 2.10-2.12 (2H, m),2.76-2.79 (2H, m, 1H, OH, s), 6.16-6.35 (3H, m), 6.45 (2H, s), 6.96 (2H,s), 7.14-7.15 (2H, m), 7.27 (1H, m), 7.45 (1H, s), 8.16 (1H, s).

EXAMPLE 445-{2-[3-(7-Hydroxy-1-methoxy-1,7-dimethyloctyl)phenyl]-vinyl}benzene-1,3-diol

a) 1,3-bis-Ethoxymethoxy-5-vinylbenzene.

At 0° C., 18 ml (36 mmol) of phenyllithium 2M/cyclohexane-ether areadded, dropwise, to 14.3 g (0.04 mol) of methyltriphenylphosphoniumbromide. The solution is stirred at room temperature for 4 h 30 min. Itis then cooled to −70° C. and 5.10 g (0.02 mol) of3,5-bis-ethoxymethoxybenzaldehyde in 50 ml of THF are added dropwise.The medium is stirred for 2 h at −70° C. and then at room temperaturefor 12 h. It is then poured into a saturated aqueous ammonium chloridesolution and extracted with ether. The organic phase is washed withwater, dried over magnesium sulphate and concentrated. The residue ispurified on a silica column (dichloromethane 30-heptane 70).

Yellow oil. m=4.4 g. Y=87%. ¹H NMR (CDCl₃): 1.20-1.25 (6H, t), 3.68-3.77(4H, q), 5.22 (4H, s), 5.69-5.76 (1H, dd, J=16.9 Hz, J′=0.55 Hz),6.58-6.69 (2H, m), 6.75-6.76 (2H, d).

b) 1-{3-[2-{3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}ethanone.

In a manner similar to Example 40(a), by reacting 2.5 g (12.5 mmol) of3-bromoacetophenone in 100 ml of dimethylformamide with 3.47 g (13.7mmol) of 1,3-bis-ethoxymethoxy-5-vinylbenzene and 3.47 g (25 mmol) ofpotassium carbonate and as catalyst 408 mg (0.5 mmol) of[1,1′-bis-(diphenylphosphino)ferrocene]-dichloropalladium, afterpurification on a silica column (ethyl acetate 15-heptane 85), a yellowoil (m=3.88 g; Y=84%) is obtained.

¹H NMR (CDCl₃): 1.22-1.28 (6H, t), 2.64 (3H, s), 3.71-3.80 (4H, m), 5.25(4H, s), 6.68-6.70 (1H, t), 6.88-6.89 (2H, d), 7.11 (2H, s), 7.42-7.48(1H, t), 7.68-7.71 (1H, d, J=7.8 Hz), 7.82-7.85 (1H, d, J=20 7.7 Hz),8.08 (1H, s)

c)2-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-8-methyl-8-(tetrahydropyran-2-yloxy)nonan-2-ol.

In a manner similar to Example 8(j), by reacting 1.85 g (5 mmol) of1-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}ethanone with thesolution of 344 mg (13.7 mmol) of magnesium, 3.67 g (12.5 mmol) of2-(6-bromo-1,1-dimethylhexyloxy)tetrahydropyran in 12 ml of THF andcatalysed by 107 mg (0.2 mmol) of[1,2-bis-(diphenylphosphino)ethane]-dichloronickel, after purificationon a silica column (ethyl acetate 15-heptane 85), a yellow oil (m=1.16g; Y=40%) is obtained.

¹H NMR (CDCl₃): 1.14-1.16 (6H, d), 1.22-1.27 (6H, m), 1.58 (3H, s),1.39-1.81 (16H, m), 3.38-3.43 (1H, m), 3.71-3.79 (4H, m), 4.89-4.94 (1H,m), 4.66 (1H, m), 5.24 (4H, s), 6.65-6.67 (1H, t), 6.87-6.88 (2H, d),7.01-7.15 (2H, dd, J=16.3 Hz, J′=2.4 Hz), 7.30-7.39 (3H, m), 7.58 (1H,s).

d)5-{2-[3-(7-Hydroxy-1-methoxy-1,7-dimethyloctyl)phenyl]vinyl}benzene-1,3-diol

In a manner similar to Example 1(j), by reacting 0.2 ml of concentratedsulphuric acid in 3 ml of methanol with 350 mg (0.6 mmol) of2-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-8-methyl-8-(tetrahydropyran-2-yloxy)nonan-2-olin 3 ml of methanol and 3 ml of THF, after purification on a silicacolumn (ethyl acetate 60-heptane 40), white crystals (m=76 mg; Y=32%)are obtained. m.p.=65-75° C.

¹H NMR (acetone): 0.91 (6H, s), 1.03-1.16 (8H, m), 1.34 (3H, s), 1.59(2H, m), 2.70 (2H, OH, s), 2.88 (3H, s), 6.11 (1H, s), 6.40-6.41 (2H,d), 6.93 (2H, s), 7.12-07.18 (2H, m), 7.26-7.29 (1H, d, J=6.8 Hz), 7.39(1H, s), 8.11 (1H, s).

EXAMPLE 455-{2-[3-(6-Hydroxy-1-methoxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol

a)2-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-7-methyl-7-(tetrahydropyran-2-yloxy)octan-2-ol.

In a manner similar to Example 8(j), by reacting 1.18 g (3.18 mmol) of1-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}ethanone with asolution of 213 mg (8.75 mmol) of magnesium, 2.15 g (7.7 mmol) of2-(5-bromo-1,1-dimethylpentyloxy)tetrahydropyran in 8 ml of THF andcatalysed by 68 mg (0.13 mmol) of[1,2-bis-(diphenylphosphino)ethane]-dichloronickel, after purificationon a silica column (ethyl acetate 25-heptane 75), a yellow oil (m=768mg; Y=42%) is obtained.

¹H NMR (CDCl₃): 0.94-0.96 (6H, d), 1.02-1.09 (6H, m), 1.38 (3H, s),1.21-1.64 (14H, m), 3.18-3.25 (1H, m), 3.51-3.60 (4H, m), 3.69-3.74 (1H,m), 4.46-4.48 (1H, m), 5.04 (4H, s), 6.46-6.47 (1H, t), 6.67-6.68 (2H,d), 6.81-6.95 (2H, dd, J=16.4 Hz, J′=2.4 Hz), 7.11-7.19 (3H, m), 7.38(1H, s).

b)5-{2-[3-(6-Hydroxy-1-methoxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol

In a manner similar to Example 1(j), by reacting 0.2 ml of concentratedsulphuric acid in 3 ml of methanol with 340 mg (0.6 mmol) of2-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-7-methyl-7-(tetrahydropyran-2-yloxy)octan-2-olin 3 ml of methanol and 3 ml of THF, after purification on a silicacolumn (ethyl acetate 60-heptane 40), white crystals (m=72 mg; Y=32%)are obtained. m.p.=65-75° C.

¹H NMR (CDCl₃): 1.17 (6H, s), 1.26-1.40 (6H, m), 1.55 (3H, s), 1.76-1.82(2H, t), 3.10 (3H, s), 6.35 (1H, t), 6.60-6.61 (2H, d), 6.93-7.09 (2H,dd, J=16.3 Hz, J′=5 Hz), 7.20-7.39 (5H, m), 7.47 (1H, s).

EXAMPLE 46 5-{2-[3-(5-Hydroxypentyl)phenyl]vinyl}benzene-1,3-diol

a) Methyl 5-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]phenyl}pentanoate.

In a manner similar to Example 1(h), by reacting 1.54 g (3.77 mmol) of3-bromo-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl in 15 ml ofdimethylformamide with the solution, at 0° C., of 1.61 g (6.6 mmol) of9-borabicyclo[3.3.1]nonane in 40 ml of THF and 502 mg (4.4 mmol) ofmethyl pent-4-enoate in 10 ml of THF, after purification on a silicacolumn (ethyl acetate 15-heptane 85), a yellow oil (m=1.19 g; Y=71%) isobtained.

¹H NMR (CDCl₃): 1.21-1.27 (6H, t), 1.33-1.87 (4H, m), 2.32-2.38 (2H, t),2.64 (2H, t), 3.66 (3H, s), 3.70-3.84 (4H, m), 5.24 (4H, s), 6.65-6.67(1H, t), 6.86-6.87 (2H, d), 7.03-7.09 (3H, m), 7.23-7.34 (3H, m).

b) 5-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}pentan-1-ol.

In a manner similar to Example 1(e), by reacting 5 ml ofdiisobutylaluminium hydride 1M/toluene, at −78° C., with 738 mg (1.67mmol) of methyl5-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-pentanoate, afterpurification on a silica column (ethyl acetate 40-heptane 60), a yellowoil (m=259 mg; Y=37%) is obtained.

¹H NMR (CDCl₃): 1.21-1.27 (6H, t), 1.38-1.84 (6H, m), 2.61-2.67 (2H, t),3.62-3.67 (2H, t), 3.70-3.85 (4H, m), 5.24 (4H, s), 6.65-6.67 (1H, t),6.86-6.87 (2H, d), 7.03-7.09 (3H, m), 7.22-7.31 (3H, m).

c) 5-{2-[3-(5-Hydroxypentyl)phenyl]vinyl}benzene-1,3-diol.

In a manner similar to Example 1(j), by reacting 0.1 ml of concentratedsulphuric acid in 1 ml of methanol with 90 mg (0.2 mmol) of5-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}pentan-1-ol in 1 ml ofmethanol and 1 ml of THF, after purification on a silica column (ethylacetate 60-heptane 40), a white powder (m=33 mg; Y=55%) is obtained.

m.p.=144-6° C. ¹H NMR (CDCl₃): 1.46-1.80 (6H, m), 2.68-2.74 (2H, t),3.58-3.63 (2H, m), 6.38-6.39 (1H, t), 6.66 (2H, d), 7.16 (3H, s),7.30-7.36 (1H, t), 7.44-7.50 (2H, m), 8.37 (1H, OH, s).

EXAMPLE 475-{2-[3-(5-Hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol

a) 5-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}pentanal.

586 mg (1.55 mmol) of pyridinium dichromate are added to a solution of162 mg (0.39 mmol) of5-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}pentan-1-ol in 2 ml ofdichloromethane. The reaction medium is stirred overnight at roomtemperature. After evaporation, the residue is purified on a silicacolumn (dichloromethane).

Yellowish oil. m=76 mg. Y=47%. ¹H NMR (CDCl₃): 1.21-1.27 (6H, t),1.66-1.72 (4H, m), 2.47 (2H, m), 2.65 (2H, m), 3.71-3.79 (4H, m), 5.24(4H, s), 6.65-6.67 (1H, t), 6.86-6.87 (2H, d), 7.04-7.08 (3H, m),7.20-7.35 (3H, m), 9.76-9.77 (1H, t).

b)7-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-2-methylheptan-3-ol.

0.18 ml (0.38 mmol) of 2M isopropylmagnesium chloride are added to 74 mg(0.18 mmol) of5-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}pentanal in 1.5 ml ofether. The medium is heated at 30-35° C. overnight. It is then pouredinto an ether/water mixture. After decantation, the organic phase iswashed with a 1N hydrochloric acid solution and then with water. It isthen dried over magnesium sulphate and concentrated. The residue ispurified on a silica column (ethyl acetate 20-heptane 80).

Yellowish oil. m=62 mg. Y=75%. ¹H NMR (CDCl₃): 0.89-0.93 (6H, dd),1.22-1.27 (6H, t), 1.39-1.69 (6H, m), 2.61-2.67 (2H, t), 3.37 (1H, m),3.71-3.79 (4H, m), 5.24 (4H, s), 6.66-6.67 (1H, t), 6.86-6.87 (2H, d),6.97-7.09 (3H, m), 7.23-7.31 (3H, m).

c) 5-{2-[3-(5-Hydroxy-6-methylheptyl)phenyl]vinyl}-benzene-1,3-diol.

In a manner similar to Example 1(j), by reacting 0.1 ml of concentratedsulphuric acid in 1 ml of methanol with 60 mg (0.13 mmol) of7-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-2-methylheptan-3-olin 1 ml of methanol and 1 ml of THF, after purification on a silicacolumn (ethyl acetate 40-heptane 60), a yellowish oil (m=7 mg; Y=16%) isobtained.

¹H NMR (CDCl₃): 0.90-0.93 (6H, d), 1.43-1.81 (6H, m), 2.60-2.66 (2H, t),3.38 (1H, m), 6.32-6.38 (3H, m), 6.58 (2H, s), 6.90-7.05 (2H, dd, J=16.3Hz, J′=4.8 Hz), 7.05-7.08 (1H, d, J=7.8 Hz), 7.21-7.27 (3H, m).

EXAMPLE 485-{2-[3-(6-Hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol

a) Methyl 6-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]phenyl}hexanoate.

In a manner similar to Example 1(h), by reacting 1.50 g (3.68 mmol) of3-bromo-[2-{3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl in 30 ml ofdimethylformamide with the solution, at 0° C., of 1.61 g (6.6 mmol) of9-borabicyclo[3.3.1]nonane in 30 ml of THF and 564 mg (4.4 mmol) ofmethyl hex-5-enoate in 10 ml of THF, after purification on a silicacolumn (ethyl acetate 10-heptane 90), a yellowish oil (m=430 mg; Y=26%)is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 1.34-1.87 (6H, m), 2.29-2.35 (2H, t),2.59-2.65 (2H, t), 3.66 (3H, s), 3.71-3.81 (4H, m), 5.24 (4H, s),6.65-6.67 (1H, t), 6.86-6.87 (2H, d), 6.97-7.11 (3H, m), 7.23-7.34 (3H,m).

b) 6-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}hexan-1-ol.

In a manner similar to Example 1(e), by reacting 2.1 ml ofdiisobutylaluminium hydride 1M/toluene, at −78° C., with 315 mg (0.69mmol) of methyl6-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]-phenyl}hexanoate, afterpurification on a silica column (ethyl acetate 40-heptane 60), a yellowpaste (m=198 mg; Y=66%) is obtained.

¹H NMR (CDCl₃): 1.21-1.27 (6H, t), 1.38-1.40 (4H, m), 1.52-1.68 (4H, m),2.59-2.65 (2H, t), 3.61-3.66 (2H, t), 3.70-3.85 (4H, m), 5.24 (4H, s),6.66-6.67 (1H, t), 6.86-6.87 (2H, d), 6.97-7.11 (3H, m), 7.22-7.33 (3H,m).

c) 6-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}hexanal.

In a manner similar to Example 47(a), by reacting 692 mg (1.83 mmol) ofpyridinium dichromate with 197 mg (0.46 mmol) of6-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}hexan-1-ol in 3 ml ofdichloromethane, after purification on a silica column(dichloromethane), a yellow paste (m=76 mg; Y=75%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 1.39-1.45 (2H, m), 1.62-1.73 (4H, m),2.40-2.46 (2H, m), 2.60-2.66 (2H, t), 3.71-3.80 (4H, m), 5.24 (4H, s),6.65-6.67 (1H, t), 6.86-6.87 (2H, d), 6.97-7.12 (3H, m), 7.20-7.34 (3H,m), 9.76 (1H, t).

d)8-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-2-methyloctan-3-ol.

In a manner similar to Example 47(b), by reacting 0.35 ml (0.7 mmol) ofisopropylmagnesium chloride 2M/ether with 148 mg (0.35 mmol) of6-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}hexanal in 2 ml ofether, after purification on a silica column (ethyl acetate 15-heptane85), a yellow oil (m=130 mg; Y=79%) is obtained.

¹H NMR (CDCl₃): 0.88-0.92 (6H, dd), 1.22-1.27 (6H, t), 1.37-1.68 (8H,m), 2.60-2.66 (2H, t), 3.35 (1H, m), 3.71-3.79 (4H, m), 5.24 (4H, s),6.66-6.67 (1H, t), 6.86-6.87 (2H, d), 6.97-7.09 (3H, m), 7.23-7.31 (3H,m).

e) 5-{2-[3-(6-Hydroxy-7-methyloctyl)phenyl]vinyl}-benzene-1,3-diol.

In a manner similar to Example 1(j), by reacting 0.2 ml of concentratedsulphuric acid in 1 ml of methanol with 130 mg (0.27 mmol) of8-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-2-methyloctan-3-ol in1 ml of methanol and 1 ml of THF, after purification on a silica column(ethyl acetate 40-heptane 60), a yellowish oil (m=12 mg; Y=13%) isobtained.

¹H NMR (CDCl₃): 0.90-0.93 (6H, d), 1.36-2.17 (8H, m), 2.57-2.63 (2H, t),3.38 (1H, m), 6.34-6.38 (1H, t), 6.58-6.59 (2H, d), 6.89-7.04 (2H, dd,J=16.3 Hz, J′=3.6 Hz), 7.04-7.06 (1H, d, J=6.9 Hz), 7.14-7.29 (3H, m).

EXAMPLE 495-{2-[3-(5-Hydroxy-6-methylhept-1-enyl)phenyl]vinyl}-benzene-1,3-diol

a) Methyl5-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]phenyl}pent-4-enoate.

In a manner similar to Example 40(a), by reacting 1.5 g (3.68 mmol) of3-bromo-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl in 30 ml ofdimethylformamide with 502 mg (4.4 mmol) of methyl pent-4-enoate and1.02 g (7.36 mmol) of potassium carbonate and as catalyst 120 mg (0.15mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium, afterpurification on a silica column (ethyl acetate 10-heptane 90), a yellowpaste (m=883 mg; Y=54%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 2.47-2.59 (4H, m), 3.70 (3H, s),3.67-3.79 (4H, q), 5.24 (4H, s), 6.19-6.30 (1H, m), 6.42-6.48 (1H, d,J=15.9 Hz), 6.66-6.67 (1H, t), 6.86-6.87 (2H, d, J=2.1 Hz), 7.04 (2H,s), 7.21-7.37 (3H, m), 7.46 (1H, s).

b) 5-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}pent-4-en-1-ol.

In a manner similar to Example 1(e), by reacting 6 ml ofdiisobutylaluminium hydride 1M/toluene, at −78° C., with 869 mg (1.97mmol) of methyl5-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}pent-4-enoate in 20 mlof toluene, after purification on a silica column (ethyl acetate30-heptane 70), a yellow paste (m=381 mg; Y=47%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 1.72-1.83 (2H, m), 2.29-2.38 (2H, m),3.71-3.79 (6H, m), 5.24 (4H, s), 6.22-6.34 (1H, m), 6.41-6.47 (1H, d,J=15.9 Hz), 6.66-6.67 (1H, t), 6.86-6.87 (2H, d, J=1.94 Hz), 7.05 (2H,s), 7.22-7.36 (3H, m), 7.47 (1H, s).

c) 5-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}pent-4-enal.

In a manner similar to Example 47(a), by reacting 1.38 g (3.68 mmol) ofpyridinium dichromate with 380 mg (0.92 mmol) of5-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}pent-4-en-1-ol in 10ml of dichloromethane, after purification on a silica column(dichloromethane), a yellow paste (m=245 mg; Y=65%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 2.56-2.66 (4H, m), 3.71-3.79 (4H, q),5.24 (4H, s), 6.19-6.31 (1H, m), 6.42-6.48. (1H, d, J=15.9 Hz),6.66-6.68 (1H, t), 6.86-6.87 (2H, d, J=2.1 Hz), 7.04 (2H, s), 7.20-7.37(3H, m), 7.46 (1H, s), 9.84 (1H, s).

d)7-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-2-methylhept-6-en-3-ol.

In a manner similar to Example 47(b), by reacting 0.58 ml (1.16 mmol) ofisopropylmagnesium chloride 2M/ether with 239 mg (0.58 mmol) of5-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}pent-4-enal in 2.5 mlof ether, after purification on a silica column (ethyl acetate15-heptane 85), a yellow oil (m=137 mg; Y=52%) is obtained.

¹H NMR (CDCl₃): 0.92-0.94 (6H, m), 1.25 (6H, s), 1.62-1.73 (2H, m),2.26-2.45 (2H, m), 3.44 (1H, m), 3.71-3.79 (4H, q), 5.24 (4H, s),6.24-6.35 (1H, m), 6.42-6.48 (1H, d, J=15.9 Hz), 6.66-6.67 (1H, t),6.86-6.87 (2H, d, J=2.08 Hz), 7.05 (2H, s), 7.22-7.36 (3H, m), 7.47 (1H,s).

e)5-{2-[3-(5-Hydroxy-6-methylhept-1-enyl)phenyl]-vinyl}benzene-1,3-diol.

In a manner similar to Example 1(j), by reacting 0.3 ml of concentratedsulphuric acid in 2.8 ml of methanol with 140 mg (0.31 mmol) of7-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-2-methylhept-6-en-3-olin 2.8 ml of THF, after purification on a silica column (ethyl acetate40-heptane 60), a white powder (m=80 mg; Y=77%) is obtained. m.p.=51-60°C.

¹H NMR (CDCl₃): 0.85-0.88 (6H, d), 1.58-1.63 (2H, m), 2.23-2.37 (2H, m),3.37-3.46 (1H, m), 6.16-6.37 (3H, m), 6.52 (2H, s), 6.88 (2H, m),7.13-7.22 (3H, m), 7.31 (2H, s).

EXAMPLE 505-{2-[3-(6-Hydroxy-7-methyloct-1-enyl)phenyl]-vinyl}benzene-1,3-diol

a) 6-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}hex-5-en-1-ol.

In a manner similar to Example 1(e), by reacting 3.9 ml ofdiisobutylaluminium hydride 1M/toluene, at −78° C., with 581 mg (1.28mmol) of methyl6-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}hex-5-enoate in 15 mlof toluene, after purification on a silica column (ethyl acetate30-heptane 70), a yellow oil (m=290 mg; Y=53%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 1.57-1.68 (4H, m), 2.23-2.31 (2H, m),3.71-3.79 (6H, m), 5.24 (4H, s), 6.20-6.32 (1H, m), 6.38-6.45 (1H, d,J=15.9 Hz), 6.66-6.67 (1H, t), 6.86-6.87 (2H, d, J=2 Hz), 7.05 (2H, s),7.22-7.36 (3H, m), 7.47 (1H, s).

b) 6-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}hex-5-enal.

In a manner similar to example 47(a), by reacting 1.02 g (2.7 mmol) ofpyridinium dichromate with 290 mg (0.68 mmol) of6-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}hex-5-en-1-ol in 10 mlof dichloromethane, after purification on a silica column(dichloromethane), a yellowish paste (m=202 mg; Y=70%) is obtained.

¹H NMR (CDCl₃): 1.22-1.27 (6H, t), 1.78-1.90 (2H, m), 2.24-2.33 (2H, m),2.49-2.54 (2H, m), 3.71-3.79 (4H, q), 5.24 (4H, s), 6.16-6.28 (1H, m),6.39-6.45 (1H, d, J=15.9 Hz), 6.66-6.68 (1H, t), 6.87 (2H, d, J=2.1 Hz),7.05 (2H, s), 7.20-7.37 (3H, m), 7.47 (1H, s), 9.80 (1H, s).

c)8-{3-[2-(3,5-bis-Ethoxymethoxyphenyl)vinyl]-phenyl}-2-methyloct-7-en-3-ol.

In a manner similar to Example 47(b), by reacting 0.47 ml (0.94 mmol) ofisopropylmagnesium chloride 2M/ether with 198 mg (0.47 mmol) of6-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}hex-5-enal in 2 ml ofether, after purification on a silica column (ethyl acetate 15-heptane85), a yellow oil (m=107 mg; Y=49%) is obtained.

¹H NMR (CDCl₃): 0.90-0.94 (6H, dd) 1.22-1.27 (6H, t) 1.42-1.74 (4H, m),2.23-2.28 (2H, m), 3.40 (1H, s), 3.71-3.79 (4H, q), 5.24 (4H, s),6.21-6.33 (1H, m), 6.38-6.44 (1H, d, J=15.9 Hz), 6.66-6.67 (1H, t),6.86-6.87 (2H, d, J=2.1 Hz), 7.05 (2H, s), 7.22-7.36 (3H, m), 7.47 (1H,s).

d) 5-{2-[3-(6-Hydroxy-7-methyloct-1-enyl)phenyl]-vinyl}benzene-1,3-diol.

In a manner similar to Example 1(j), by reacting 0.3 ml of concentratedsulphuric acid in 2.5 ml of methanol with 126 mg (0.27 mmol) of8-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl]phenyl}-2-methyloct-7-en-3-olin 2.5 ml of THF, after purification on a silica column (ethyl acetate40-heptane 60), a beige powder (m=60 mg; Y=63%) is obtained.

m.p.=115-20° C. ¹H NMR (CDCl₃): 0.91-0.94 (6H, d), 1.50-1.69 (4H, m),2.24 (2H, m), 3.43-3.54 (1H, m), 6.17-6.40 (3H, m), 6.59 (2H, s), 6.95(2H, s), 7.20-7.31 (3H, m), 7.38 (1H, s), 7.59 (2H, s).

EXAMPLE 515-{2-[3-(1,6-Dihydroxy-1,6-dimethylheptyl)phenyl]-vinyl}benzene-1,3-diol

In a manner similar to Example 1(j), by reacting 0.6 ml of concentratedsulphuric acid in 7.5 ml of methanol with 369 mg (0.65 mmol) of2-{3-[2-(3,5-bis-ethoxymethoxyphenyl)vinyl}phenyl}-7-methyl-7-(tetrahydropyran-2-yloxy)octan-2-olin 7.4 ml of THF, after purification on a silica column (ethyl acetate70-heptane 30), a yellowish paste (m=220 mg; Y=92%) is obtained.

¹H NMR (CDCl₃): 1.16 (6H, s), 1.28-1.39 (6H, m), 1.57 (3H, s), 1.77-1.84(2H, m), 6.35-6.37 (1H, t), 6.58-6.59 (2H, d), 6.92-7.06 (2H, dd, J=16.4Hz), 2.4 Hz), 7.27-7.38 (3H, m), 7.59 (1H, s), 7.83 (2H, OH, s).

EXAMPLE 525-{2-[3-(6-Hydroxy-1,6-dimethylhept-1-enyl)phenyl]-vinyl}benzene-1,3-diol

In a manner similar to Example 1(j), by reacting 0.09 ml of concentratedsulphuric acid in 3 ml of THF with 152 mg (0.41 mmol) of5-{2-[3-(1,6-dihydroxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diolin 1.5 ml of THF, after purification on a silica column (ethyl acetate50-heptane 50), a yellow powder (m=65 mg; Y=45%) is obtained.m.p.=55-60° C.

¹H NMR (CDCl₃): 1.21 (3H, s), 1.24 (6H, s), 1.45-1.55 (4H, m), 2.23 (1H,m), 2.54 (1H, m), 5.80 (1H, t), 6.34 (1H, s), 6.59 (2H, s), 6.92-7.08(2H, dd, J=16.3 Hz, J′=6 Hz), 7.28-7.33 (3H, m), 7.45 (1H, m).

EXAMPLE 536-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-methylamino}-2-methylhexan-2-ol

a) Ethyl6-{[3-(p-Toluenesulphonyloxy)phenyl]carbomethoxyamino}pentanoate.

1 g (3.1 mmol) of 3-p-toluenesulphonyloxy-N-carbomethoxyaniline and 1.9ml (12 mmol) of ethyl 5-bromovalerate are dissolved in 25 ml ofanhydrous DMF. 140 mg (4.5 mmol) of 75% sodium hydride are then addedand the reaction medium is stirred for 6 hours. After treating with asaturated ammonium chloride solution and extracting with dichloromethaneand then drying and evaporating the solvents of the organic phase, theresidue is purified by chromatography on a silica column. A colourlessoil is obtained (m=1.35 g; Y=97%).

b)6-{[3-(p-Toluenesulphonyloxy)phenyl]carbomethoxyamino}-2-methylhexan-2-ol.

500 mg of ethyl6-{[3-(p-toluenesulphonyloxy)phenyl]carbomethoxyamino}pentanoate (1.2mmol) are dissolved in 20 ml of THF. 1 ml of a 3.0 M solution ofmethylmagnesium bromide (3.0 mmol) is then added and the reaction mediumis stirred for 1 hour at room temperature. After treating with asaturated ammonium chloride solution, drying and evaporating thesolvents of the organic phase and then purifying by chromatography on asilica column, a colourless oil is obtained (m=480 mg; Y=92%).

c) 6-[(3-Hydroxyphenyl)methylamino]-2-methylhexan-2-ol.

300 mg of6-{[3-(p-toluenesulphonyloxy)phenyl]carbomethoxyamino}-2-methylhexan-2-ol(0.69 mmol) are dissolved in 10 ml of anhydrous THF. 80 mg (2.1 mmol) oflithium aluminium hydride are then added, and the reaction medium isheated under reflux for two hours. After cooling, 80 l of water and then80 l of a 15% NaOH solution and then 240 l of water are addedsequentially; after stirring for 1 h, the reaction medium is thenfiltered and then the solvent is evaporated. The residue obtained isthen dissolved in a mixture composed of 5 ml of water and 5 ml ofethanol, and 200 mg of KOH are added. The reaction medium is then heatedfor 12 hours at 70° C. and then cooled and treated with a mixture of 1NHCl and dichloromethane. After separation, the organic phase is thendried and the solvents are evaporated. After purification bychromatography on a silica column, a colourless oil (m=125 mg; Y=79%) isobtained.

d)6-{[3-(3,4-bis-Carboxymethylbenzyloxy)phenyl]-methylamino}-2-methylhexan-2-ol.

90 mg (0.38 mmol) of 6-[(3-hydroxyphenyl)methylamino-2-methylhexan-2-olare added to a solution of 3-(3,4-dicarboxymethyl)benzyl bromide (132mg, 0.46 mmol) in 2-butanone. 64 mg (0.46 mmol) of potassium carbonateare then added before heating the reaction medium under reflux for 6hours. After filtration and evaporation of the solvent and purificationby chromatography on a silica gel (heptane 60-ethyl acetate 40), ayellow oil is obtained (m=67 mg; Y=40%).

e)6-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-methylamino}-2-methylhexan-2-ol.

30 mg of6-{[3-(3,4-bis-carboxymethylenzyloxy)phenyl]methylamino}-2-methylhexan-2-ol(0.07 mmol) are dissolved in 3 ml of anhydrous THF and then 20 mg (1mmol) of lithium borohydride are added before heating the reactionmedium under reflux for 3 hours. After treating the reaction medium witha saturated ammonium chloride solution and then drying, evaporating andpurifying by chromatography on a silica column (heptane 30-ethyl acetate70), a clear oil is obtained (m=19 mg; Y=72%).

¹H NMR (CDCl₃): 1.19 (s, 6H), 1.26-1.59 (m, 6H), 2.89 (s, 3H), 3.27 (t,2H, J=7.2 Hz), 4.70 (s, 4H), 5.04 (s, 2H), 6.28-6.34 (m, 3H), 7.11 (t,1H, J=7.9 Hz), 7.34 (s, 2H), 7.40 (s, 1H).

EXAMPLE 545-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-methylamino}-2-methylpentan-2-ol

In a manner similar to Example 53(e), by reacting 80 mg (0.18 mmol) of5-{[3-(3,4-bis-carboxymethylbenzyloxy)phenyl]methylamino}-2-methylpentan-2-ol(prepared in a manner similar to Examples 53(a-d)) with 16 mg (0.75mmol) of lithium borohydride and after purification on a silica column,a colourless oil is obtained (m=50 mg; Y=76%).

¹H NMR (CDCl₃): 1.18 (s, 6H), 1.37-1.43 (m, 2H), 1.54-1.63 (m, 2H), 1.70(bs, 1H), 2.89 (s, 3H), 3.25 (t, 2H, J=7.4 Hz), 3.38 (bs, 2H), 4.69 (s,4H), 5.05 (s, 2H), 6.28-6.34 (m, 3H), 7.11 (t, 1H, J=8.0 Hz), 7.35 (s,2H), 7.39 (s, 1H).

EXAMPLE 556-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-methylamino}-3-ethylhexan-3-ol

In a manner similar to Example 53(e), by reacting 250 mg (0.45 mmol) of6-{[3-(3,4-bis-carboxymethylbenzyloxy)phenyl]methylamino}-3-ethylhexan-3-ol(prepared in a manner similar to Examples 53 (a-d)) with 40 mg (1.8mmol) of lithium borohydride and after purification on a silica column,a colourless oil is obtained (m=160 mg; Y=88%).

¹H NMR (CDCl₃): 0.82 (t, 6H, J=7.6 Hz), 1.26-1.56 (m, 8H), 2.89 (s, 3H),3.25 (t, 2H, J=6.9 Hz), 3.46 (bs, 2H), 4.67 (s, 4H), 5.04 (s, 2H),6.27-6.33 (m, 3H), 7.11 (t, 1H, J=8.1 Hz), 7.33 (m, 2H), 7.38 (s, 1H).

EXAMPLE 567-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]methylamino}-3-ethylheptan-3-ol

In a manner similar to Example 53(e), by reacting 370 mg (0.8 mmol) of7-{[3-(3,4-bis-carboxymethylbenzyloxy)phenyl]methylamino}-3-ethylheptan-3-ol(prepared in a manner similar to Examples 53 (a-d)) with 80 mg (3.5mmol) of lithium borohydride and after purification on a silica column,a colourless oil is obtained (m=266 mg; Y=80%).

¹H NMR (CDCl₃): 0.84 (t, 6H, J=7.6 Hz), 1.23-1.55 (m, 10H), 1.7 (bs,1H), 2.89 (s, 3H), 3.26 (t, 2H, J=7.6 Hz), 3.35 (bs, 2H), 4.69 (s, 2H),4.69 (s, 2H), 5.04 (s, 2H), 6.29-6.34 (m, 3H), 7.11 (t, 1H, J=8.0 Hz),7.34 (m, 2H), 7.39 (s, 1H).

EXAMPLE 575-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]ethylamino}-2-methylpentan-2-ol

a) 5-[(3-tert-Butyldimethylsilyloxyphenyl)ethylamino]-5-oxopentan-2-one.

1 g (4 mmol) of (3-tert-butyldimethylsilyloxy)-N-ethylaniline isdissolved in 40 ml of dichloromethane at 0° C. and then 511 mg (4.4mmol) of levulinic acid and 595 mg (4.4 mmol) of 1-hydroxybenzotriazoleare added to the reaction medium. 908 mg (4.4 mmol) ofdicyclohexylcarbodiimide are then added in portions. The reaction mediumis heated to room temperature, stirred for 1 hour and then filtered. Thefiltrate is then stirred for 12 h and then treated with a saturatedammonium chloride solution and extracted with dichloromethane. Afterdrying and purifying on a silica column, a colourless oil is obtained(m=1.27 g; Y=91%).

b)5-[(3-tert-Butyldimethylsilyloxyphenyl)ethylamino]-5-oxo-2-methylpentan-2-ol.

700 mg (2 mmol) of5-[(3-tert-butyldimethylsilyloxyphenyl)ethylamino]-5-oxopentan-2-one aredissolved in 20 ml of anhydrous THF and the reaction medium is cooled to0° C. 0.66 ml (2 mmol) of a methylmagnesium bromide solution is thenslowly added and the reaction medium is stirred for 4 hours at thistemperature. After treating with a saturated ammonium chloride solution,extracting with ethyl acetate, drying and then evaporating, the residueis purified by chromatography on a silica column in order to obtain acolourless oil (m=610 mg; Y=86%).

c)5-{[3-(3,4-bis-Carboxymethylbenzyloxy)phenyl]-ethylamino}-5-oxo-2-methylpentan-2-ol.

710 mg of5-[(3-tert-butyldimethylsilyloxyphenyl)ethylamino]-5-oxo-2-methylpentan-2-ol(2 mmol) are dissolved in 20 ml of THF and then 2.4 ml of atetrabutylammonium fluoride solution (1M in THF) are added dropwise.After stirring for 1 hour at room temperature, the reaction medium istreated with an ammonium chloride solution and then extracted with ethylacetate. After concentrating under reduced pressure, the residueobtained is added to a solution of 3-(3,4-dicarboxymethyl)benzyl bromide(750 mg, 2.6 mmol) in 2-butanone (25 ml). 305 mg (2.2 mmol) of potassiumcarbonate are then added before heating the reaction medium under refluxfor 6 hours. After filtration, evaporation of the solvent andpurification by chromatography on a silica gel (heptane 60-ethyl acetate40), a yellow oil is obtained (m=760 mg; Y=83%).

d)5-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-ethylamino}-2-methylpentan-2-ol.

350 mg (0.76 mmol) of5-{[3-(3,4-bis-carboxymethylbenzyloxy)phenyl]ethylamino}-5-oxo-2-methylpentan-2-olare dissolved in 10 ml of anhydrous THF and then 120 mg of lithiumaluminium hydride (3.1 mmol) are added in two equal portions. Afterheating under reflux for 4 hours, the reaction medium is cooled and thensequentially treated with 120 l of water, 120 l of a 15% NaOH solutionand then 360 l of water. After stirring for 1 hour, the reaction mediumis filtered, concentrated and then purified by chromatography on asilica gel. A colourless oil is obtained (m=280 mg; Y=95%).

¹H NMR (CDCl₃): 1.12 (t, 3H, J=7.0 Hz), 1.18 (s, 6H), 1.38-1.45 (m, 2H),1.56-1.63 (m, 3H), 3.20 (t, 2H, J=7.5 Hz), 3.31 (q, 2H, J=7.0 Hz), 4.69(s, 2H), 4.70 (s, 2H), 5.05 (s, 2H), 6.24-6.32 (m, 3H), 7.10 (t, 1H,J=8.1 Hz), 7.34 (m, 2H), 7.40 (s, 1H).

EXAMPLE 586-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]amino}-3-ethylhexan-3-ol

a)6-{[3-(3,4-bis-Carboxymethylbenzyloxy)phenyl]-N-benzoylamino}-3-ethylhexan-3-ol.

In a manner similar to Example 53(d), by reacting 130 mg (0.38 mmol) of6-[(3-hydroxyphenyl)-N-benzoylamino-3-ethylhexan-3-ol (prepared in amanner similar to Examples 53(a-c)) with a solution of3-(3,4-dicarboxymethyl)benzyl bromide (133 mg, 0.46 mmol) in 2-butanone(5 ml) and 60 mg (0.42 mmol) of potassium carbonate, after filtrationand evaporation of the solvent and purification by chromatography on asilica gel (heptane 60-ethyl acetate 40), a yellow oil is obtained(m=104 mg; Y=50%).

b)6-{[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-amino}-3-ethylhexan-3-ol.

In a manner similar to Example 57(d), by treating6-{[3-(3,4-bis-carboxymethylbenzyloxy)phenyl]-N-benzoylamino}-3-ethylhexan-3-ol(100 mg, 0.18 mmol) with 40 mg (1 mmol) of lithium aluminium hydride andafter purification on a silica column, a colourless oil is obtained(m=75 mg; Y=87%).

¹H NMR (CDCl₃): 0.86 (t, 6H, J=7.5 Hz), 1.43-1.70 (m, 9H), 3.1 (bs, 1H),3.2 (bs, 1H), 3.90 (t, 2H, J=6.3 Hz), 4.31 (s, 2H), 4.70 (s, 4H),6.14-6.28 (m, 3H), 7.04 (t, 1H, J=8.1 Hz), 7.30 (s, 2H), 7.34 (s, 1H).

EXAMPLE 59

(4E,6E)-7-{3-[2-(3,4-bis-Hydroxymethylphenyl)ethyl]-phenyl}-3-ethylocta-4,6-dien-3-ol

a) 3-(2-Methyl-[1,3]dioxolan-2-yl)benzaldehyde.

5 g (25 mmol) of 3-bromoacetophenone are dissolved in 40 ml of tolueneand then 15 ml of ethylene glycol and 500 mg of para-toluenesulphonicacid are added. The reaction medium is then heated under reflux equippedwith a Dean-Stark distillation assembly. After 12 h, the medium iscooled and then treated with water and extracted with dichloromethane.After drying and concentrating, the residue is purified on a silicacolumn in order to obtain the desired3-(2-methyl-[1,3]dioxolan-2-yl)-1-bromobenzene (Y=85%). This product (4g, 16.4 mmol) is then dissolved in anhydrous THF and the mixture iscooled to −78° C. 7.2 ml (18 mmol) of a 2.5M solution of butyllithiumare then added dropwise. After stirring for 1 hour at the sametemperature, 1.9 ml (18 mmol) of dimethylformamide are added. Themixture is maintained at −78° C. for 30 minutes and then brought to roomtemperature. The reaction medium is then treated with a saturatedammonium chloride solution and extracted with dichloromethane. Afterpurification by chromatography on a silica column (ethyl acetate10-heptane 90), a colourless oil is obtained (m=3.09 g; Y=98%).

b) Dimethyl4-{(E)-2-[3-(2-Methyl-[1,3]dioxolan-2-yl)phenyl]vinyl}phthalate.

Dimethyl 4-(diethoxyphosphorylmethyl)phthalate (2 g, 5.8 mmol) isdissolved in 30 ml of anhydrous THE and then cooled to 0° C. 2.8 ml (5.6mmol) of a 2M solution of lithium diisopropylamide are then addeddropwise and then the reaction medium is stirred at this temperature for30 minutes. Next, a solution of3-(2-methyl-[1,3]dioxolan-2-yl)benzaldehyde (1.02 g, 5.3 mmol) in 10 mlof THF is added using a small tube. The medium is then brought to roomtemperature and then stirred for 12 hours. After treating with asaturated ammonium chloride solution and extracting with ethyl acetate,the organic phase is dried and the solvents are evaporated. Afterpurification on a silica column (ethyl acetate 30-heptane 70), acolourless oil is obtained (m=1.68 g; Y=83%).

c) Dimethyl 4-{2-[3-(2-Methyl-[1,3]dioxolan-2-yl)phenyl]ethyl}phthalate.

1.8 g (4.7 mmol) of dimethyl4-{(E)-2-[3-(2-methyl-[1,3]dioxolan-2-yl)phenyl]vinyl}phthalate aredissolved in 50 ml of ethyl acetate. The solution is degassed for 30minutes and then 5% Pd/C (200 mg) are added. A hydrogen flask (1 bar) isthen attached to the assembly and the reaction medium is stirred for 4hours. The loss of fluorescence during the TLC analyses (=254 nm)indicates the end of the reaction: the reaction medium is then filteredand then concentrated under reduced pressure to give a colourless oil(m=1.78 g; Y=98%).

d) 1-{3-[2-(3,4-bis-Hydroxymethylphenyl)ethyl]-phenyl}ethanone.

Dimethyl 4-{2-[3-(2-methyl-[1,3]dioxolan-2-yl)phenyl]ethyl}phthalate(1.78 g, 4.6 mmol) is dissolved in 20 ml of anhydrous THF. 530 mg oflithium aluminium hydride (14 mmol) are then added in three equalfractions and then the reaction medium is heated under reflux for 4hours. The medium is then cooled and then sequentially treated with 530l of water, 530 l of 15% NaOH and then 1.6 ml of water. After stirringfor 1 hour, the mixture is filtered and then concentrated under reducedpressure. The residue obtained is then dissolved in 10 ml of acetone towhich 5 ml of water and 100 mg of para-toluenesulphonic acid are added.The reaction medium is stirred at 70° C. for 12 h, and then poured into50 ml of ethyl acetate. After separating and drying the organic phase,the solvents are evaporated and then the residue purified bychromatography on a silica gel (ethyl acetate 50-heptane 50) in order toobtain a white semisolid (m=1.18 g; Y=90%).

e)1-(3-{2-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenyl]ethyl}phenyl)ethanone.

1.15 g of 1-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}ethanone(4.04 mmol) are dissolved in 20 ml of DMF and 20 ml of dichloromethane.The mixture is cooled to 0° C. and then 1.7 ml of triethylamine (12mmol) are added, followed by 1.35 g of tert-butyldimethylsilane chloride(8.9 mmol). The medium is stirred at room temperature for 12 h and thentreated with a saturated ammonium chloride solution and extracted withethyl ether. The organic phase is washed with water and then dried andconcentrated under reduced pressure to give a colourless oil (m=2.07 g;Y=100%).

f) Ethyl(2E,4E)-5-(3-{2-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenyl]ethyl}phenyl)hexa-2,4-dienoate.

850 ml (3.9 mmol) of ethyl 4-diethylphosphonocrotonate are dissolved in5 ml of THF. To this mixture there are added 10 ml of DMPU(1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone) and then, aftercooling to 0° C., 1.85 ml (3.7 mmol) of a 2M solution of lithiumdiisopropylamide. The mixture is stirred for 30 minutes at this sametemperature and then a solution of 1 g (1.95 mmol) of1-(3-{2-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]ethyl}phenyl)ethanoatein 5 ml of THF is added dropwise. The mixture is then brought to roomtemperature and then stirred for 48 hours. After treating with asolution of ammonium chloride and extracting with ethyl acetate, theorganic phase is dried and concentrated under reduced pressure. Afterchromatography on a silica column, a light-yellow oil is obtained(m=1.46 g; Y=81%).

g)(4E,6E)-7-(3-{2-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenyl]ethyl}phenyl)-3-ethylocta-4,6-dien-3-ol.

500 mg of ethyl(2E,4E)-5-(3-{2-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]ethyl}-phenyl)hexa-2,4-dienoate(0.82 mmol) are dissolved in 10 ml of anhydrous THF and the mixture iscooled to −78° C. 5.4 ml (4 mmol) of a freshly prepared ethyllithiumsolution (0.75 M) are then added dropwise and then the mixture isbrought to 0° C. After stirring for 1 hour, the reaction medium istreated with a saturated ammonium chloride solution and extracted withethyl acetate. After purification by chromatography on a silica column(ethyl acetate 5-heptane 95), the pure all-trans isomer is obtained inthe form of a colourless oil (m=350 mg; Y=70%).

h)(4E,6E)-7-{3-[2-(3,4-bis-Hydroxymethylphenyl)ethyl]phenyl}-3-ethylocta-4,6-dien-3-ol.

340 mg of(4E,6E)-7-(3-{2-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl]ethyl}phenyl)-3-ethylocta-4,6-dien-3-ol(0.5 mmol) are dissolved in 10 ml of THF and 1.5 ml (1.5 mmol) of atetrabutylammonium fluoride solution (1M in THF) are added dropwise.After 30 minutes, 10 ml of methanol are added and the mixture isconcentrated under reduced pressure. After purification of the residueby chromatography on a silica column, a colourless oil is obtained(m=163 mg; Y=88%).

¹H NMR (CDCl₃): 0.90 (t, 6H, J=7.4 Hz), 1.61 (q, 4H, J=7.5 Hz), 2.17 (s,3H), 2.92 (bs, 2H), 2.92 (s, 4H), 4.71 (s, 4H), 5.77 (d, 1H, J=15.1 Hz),6.42 (d, 1H, J=11 Hz), 6.63 (dd, 1H, J1=15.1 Hz, J2=11 Hz), 7.08-7.29(m, 7H).

EXAMPLE 60(3E,5E)-6-{3-[2-(3,4-bis-Hydroxymethylphenyl)ethyl]-phenyl}-2-methylhepta-3,5-dien-2-ol

In a manner similar to Example 59(h), by reacting 410 mg (0.7 mmol) of(3E,5E)-6-{3-[2-(3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenyl)ethyl]-phenyl}-2-methylhepta-3,5-dien-2-ol(prepared in a manner similar to Examples 53(a-g)) with 2 ml (2 mmol) ofa tetrabutylammonium fluoride solution (1M in THF), a colourless oil isobtained (m=230 mg; Y=96%).

¹H NMR (CDCl₃): 1.39 (s, 6H), 2.15 (s, 3H), 2.91 (s, 4H), 2.92 (bs, 2H),4.69 (s, 2H), 4.70 (s, 2H), 5.94 (d, 1H, J=15.1 Hz), 6.36 (d, 1H, J=10.9Hz), 6.62 (dd, 1H, J1=15.1 Hz, J2=10.9 Hz), 7.06-7.28 (m, 7H).

EXAMPLE 61(4E-6E)-7-{3-[2-(3,4-bis-Hydroxymethylphenyl}vinyl]-phenyl)-3-ethylocta-4,6-dien-3-ol

In a manner similar to Example 59(h), by reacting 320 mg (0.5 mmol) of(4E,6E)-7-(3-{2-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl]-vinyl}phenyl)-3-ethylocta-4,6-dien-3-ol(prepared in a manner similar to Examples 53(a-b, d-g)) with 1.5 ml (1.5mmol) of a 1M solution of tetrabutylammonium fluoride, a colourless oilis obtained (m=184 mg; Y=100%).

¹H NMR (CDCl₃): 0.91 (t, 6H, J=7.4 Hz), 1.62 (q, 4H, J=7.4 Hz), 2.22 (s,3H), 4.13 (bs, 1H), 4.21 (bs, 1H), 4.72 (s, 2H), 4.75 (s, 2H), 5.82 (d,1H, J=14.9 Hz), 6.52 (d, 1H, J=11 Hz), 6.65 (dd, 1H, J1=14.9 Hz, J2=11Hz), 7.13 (s, 2H), 7.29-7.57 (m, 7H).

EXAMPLE 62(3E,5E)-6-{3-[2-(3,4-bis-Hydroxymethylphenyl)vinyl]-phenyl}-2-methylhepta-3,5-dien-2-ol

In a manner similar to Example 59(h), by reacting 450 mg (0.75 mmol) of(3E,5E)-6-{3-[2-(3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl)vinyl]phenyl}-2-methylhepta-3,5-dien-2-ol(prepared in a manner similar to Examples 59(a-b, d-g)) with 2 ml (2mmol) with a tetrabutylammonium fluoride solution (1M in THF), acolourless oil is obtained (m=270 mg; Y=99%).

¹H NMR (CDCl₃): 1.40 (s, 6H), 2.21 (s, 3H), 2.35 (bs, 1H), 4.20-4.40(bs, 2H), 4.71 (s, 2H), 4.74 (s, 2H), 5.98 (d, 1H, J=15 Hz), 6.47 (d,1H, J=10.9 Hz), 6.67 (dd, 1H, J1=15.0 Hz, J2=10.9 Hz), 7.13 (s, 2H),7.31-7.55 (m, 7H).

EXAMPLE 63(4E,6E)-7-[3-(3,4-bis-Hydroxymethylphenylethynyl)phenyl]-3-ethylocta-4,6-dien-3-ol

a) 1-(3-Ethynylphenyl)ethanone

4 g of 3-bromoacetophenone (20 mmol) and 4.23 ml (30 mmol) oftrimethylsilylacetylene are dissolved in 50 ml of triethylamine. CuI(760 mg, 4 mmol) are added and the reaction medium is degassed for 10minutes by an argon stream. Tetrakis(triphenylphosphine)palladium (1.4g, 2 mmol) is then added in one fraction, and the reaction medium isstirred for 12 hours at room temperature. The medium is then treatedwith water and extracted with dichloromethane. After drying andconcentrating under reduced pressure, the residue is dissolved in 100 mlof THF, to which 100 ml of ethanol and 10 ml of water are added. Twofractions of 1.4 g (24 mmol) of potassium fluoride are added at aninterval of 9 hours and then the reaction medium is stirred for 24 hbefore being concentrated under reduced pressure. The residue is thentaken up in a mixture of dichloromethane and a saturated ammoniumchloride solution. The organic phase is dried and then concentrated.After chromatography on a silica column (ethyl acetate 10-heptane 90), aclear oil is obtained (m=2.68 g; Y=93%).

b)1-{3-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenylethynyl]phenyl}ethanone.

100 mg (0.1 mmol) of tetrakis(triphenylphosphine)palladium, 35 mg (0.2mmol) of CuI and 250 mg (1.7 mmol) of 1-(3-ethynylphenyl)ethanone aresuccessively added to 850 mg (1.7 mmol) of1,2-bis(tert-butyldimethylsilanyloxymethyl)-4-iodobenzene in 6 ml ofpyrrolidine. After 30 minutes at room temperature, the reaction mediumis filtered and then the filtrate is taken up in dichloromethane andwashed with water. A yellow oil is obtained (m=770 mg; Y=89%).

c) Ethyl(2E,4E)-5-{3-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenylethynyl]phenyl}hexa-2,4-dienoate.

0.6 ml (2.7 mmol) of ethyl 4-diethylphosphonocrotonate is dissolved in20 ml of anhydrous THF and the mixture is cooled to 0° C. 1.27 ml (2.54mmol) of a 2M solution of lithium diisopropylamide are added dropwise.After stirring for 1 hour at the same temperature, a solution of 680 mg(1.34 mmol) of1-{3-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenylethynyl]phenyl}ethanonein 5 ml of THF is slowly added by means of a small tube. The reactionmedium is brought to room temperature and then stirred for 18 hours.After treating with a saturated ammonium chloride solution andextracting with ethyl acetate, the organic phase is dried andconcentrated under reduced pressure. The residue is purified bychromatography on a silica column: a yellow oil is obtained (m=480 mg;Y=60%).

d)(4E,6E)-7-[3-(3,4-bis-Hydroxymethylphenylethynyl)phenyl]-3-ethylocta-4,6-dien-3-ol.

470 mg of ethyl(2E,4E)-5-{3-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenylethynyl]phenyl}hexa-2,4-dienoate(0.77 mmol) are dissolved in 10 ml of anhydrous THF. 0.8 ml (2.4 mmol)of a 3M solution of ethylmagnesium bromide are added dropwise. After 30minutes at room temperature, the reaction medium is treated with anammonium chloride solution and then extracted with ethyl acetate. Theresidue, obtained after drying and concentrating the organic phase, isthen dissolved in 10 ml of THF and 3 ml (3 mmol) of a tetrabutylammoniumfluoride solution (1M in THF) are added. After 15 minutes, the reactionmedium is diluted with 10 ml of ethanol and then concentrated underreduced pressure. The residue is purified by chromatography on a silicagel (ethyl acetate 40-heptane 60). A colourless oil is obtained (m=55mg; Y=18%).

¹H NMR (CDCl₃): 0.93 (t, 6H, J=6.7 Hz), 1.58 (q, 4H, J=6.7 Hz), 2.07 (s,3H), 2.92 (bs, 2H), 4.75 (s, 4H), 5.81 (d, 1H, J=14.8 Hz), 6.51 (d, 1H,J=10.9 Hz), 6.65 (dd, 1H, J1=14.8 Hz, J2=10.9 Hz), 7.26-7.62 (m, 7H).

EXAMPLE 647-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol

a) Ethyl 5-[3-(tert-Butyldimethylsilanyloxy)phenyl]-hexa-2,4-dienoate.

4.3 g of ethyl 4-diethylphosphonocrotonate are added dropwise to asolution of 19 mmol of lithium diisopropylamide in 150 ml of anhydrousTHF cooled to 0° C. After stirring for 1 hour at this temperature, 2 g(8 mmol) of 3-(tert-butyldimethylsilanyloxy)acetophenone dissolved in 20ml of THF are added dropwise by means of a small tube. The reactionmedium is brought to room temperature and stirred for 15 hours. Aftertreating with a saturated ammonium chloride solution and extracting withdichloromethane, the organic phase is dried and concentrated underreduced pressure. The residue is purified by chromatography on a silicacolumn. A yellow oil is obtained (m=1.39 g; Y=50%).

b) Ethyl 5-[3-(tert-Butyldimethylsilanyloxy)phenyl]-hexanoate.

600 mg (1.7 mmol) of ethyl5-[3-(tert-butyldimethylsilanyloxy)phenyl]hexa-2,4-dienoate aredissolved in 40 ml of ethyl acetate and the solution is degassed with anargon stream for 10 minutes. 100 mg of 5% Pd/C are then added and thereaction medium is equipped with a hydrogen flask (1 bar). After 6 hoursat room temperature, the reaction medium is filtered on a celite pad andthen the filtrate is concentrated under reduced pressure to give acolourless oil (m=580 mg; Y=97%).

c) 3-(5-Ethyl-5-hydroxy-1-methylheptyl)phenol.

580 mg (1.66 mmol) of ethyl5-[3-(tert-butyldimethylsilanyloxy)phenyl]hexanoate are dissolved in 25ml of ethyl ether and the mixture is cooled to 0° C. 1.9 ml of a 3Methylmagnesium bromide solution (5.8 mmol) are then added dropwise andthe medium is stirred for 3 hours. After treating with a saturatedammonium chloride solution and extracted with ethyl ether, the organicphase is dried and then concentrated under reduced pressure. Thereaction medium is then dissolved in 20 ml of THF and then 2.5 ml (2.5mmol) of a tetrabutylammonium fluoride solution (1M in THF) are added inone portion and the reaction medium is stirred for 1 hour at roomtemperature. The reaction medium is then concentrated under reducedpressure and the residue is purified by chromatography on a silicacolumn. A colourless oil is obtained (m=400 mg; Y=96%).

d) Dimethyl4-[3-(5-Ethyl-5-hydroxy-1-methylheptyl)phenoxymethyl]phthalate.

450 mg of 3-(5-ethyl-5-hydroxy-1-methylheptyl)phenol (1.8 mmol) and 620mg (2.16 mmol) of dimethyl 4-bromomethylphthalate are dissolved in 20 mlof 2-butanone. A catalytic quantity of 18-crown-6 is added, followed by300 mg (2.16 mmol) of potassium carbonate. The reaction medium is heatedunder reflux for 15 h and then cooled and filtered. The filtrate isconcentrated under reduced pressure and then the residue is purified bychromatography on a silica column. A yellow oil is obtained (m=220 mg;Y=27%).

e) 7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol.

220 mg (0.48 mmol) of dimethyl4-[3-(5-ethyl-5-hydroxy-1-methylheptyl)phenoxymethyl]phthalate aredissolved in 15 ml of anhydrous THF. 42 mg (1.9 mmol) of lithiumborohydride are then added and the reaction medium is heated underreflux for 12 hours. After cooling, treating with a saturated ammoniumchloride solution and extracting with ethyl acetate, the organic phaseis dried and concentrated under reduced pressure. The residue is thenpurified by chromatography on a silica column. A colourless oil isobtained (m=132 mg; Y=75%).

¹H NMR (CDCl₃): 0.79 (t, 6H, J=7.5 Hz), 1.13-1.57 (m, 13H), 1.72 (bs,1H), 1.65 (m, 1H), 3.44 (bs, 2H), 4.69 (s, 2H), 4.70 (s, 2H), 5.06 (s,2H), 6.77-6.79 (m, 3H), 7.19 (t, 1H, J=8.5 Hz), 7.31-7.35 (m, 2H), 7.40(s, 1H).

EXAMPLE 65(4E,6E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol

a) 7-[3-(tert-Butyldimethylsilanyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol.

In a manner similar to Example 63(d), by reacting 700 mg (2 mmol) ofethyl 5-[3-(tert-butyldimethylsilanyloxy)phenyl]hexa-2,4-dienoate(prepared in Example 64(a)) with 2.7 ml (8 mmol) of an ethylmagnesiumbromide solution (3M), 121 mg (17%) of(Z)-7-[3-(tert-butyldimethylsilanyloxy)phenyl]-3-ethylocta-4,6-dien-3-oland 146 mg (20%) of(E)-7-[3-(tert-butyldimethylsilanyloxy)phenyl]-3-ethylocta-4,6-dien-3-olare obtained after purification on a silica column (pentane-ethylacetate 90-10).

b) (4E,6E)-7-[3-Hydroxyphenyl]-3-ethylocta-4,6-dien-3-ol.

In a manner similar to Example 59(h), starting with 205 mg (0.57 mmol)of(E)-7-[3-(tert-butyldimethylsilanyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol,140 mg (100%) of expected product are obtained in the form of an oil.

c) Dimethyl4-[3-((1E,3E)-5-Ethyl-5-hydroxy-1-methylhepta-1,3-dienyl)phenoxymethyl]phthalate.

In a manner similar to Example 64(d), by reacting 140 mg (0.57 mmol) ofthe previous product with 196 mg (0.68 mmol) of dimethyl4-bromomethylphthalate, 154 mg (60%) of expected product are obtained inthe form of an oil.

d)(4E,6E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol.

In a manner similar to Example 53(e), by reacting 150 mg (0.34 mmol) ofdimethyl4-[3-((1E,3E)-5-ethyl-5-hydroxy-1-methylhepta-1,3-dienyl)phenoxymethyl]phthalatewith 30 mg (1.35 mmol) of lithium borohydride, a colourless oil isobtained (m=56 mg; Y=42%).

¹H NMR (CDCl₃): 0.89 (t, 6H, J=7.5 Hz), 1.59 (q, 4H, J=7.5 Hz), 2.15 (s,3H), 3.57 (bs, 2H), 4.66 (s, 2H), 4.67 (s, 2H), 5.03 (s, 2H), 5.76 (d,1H, J=14.9 Hz), 6.46 (d, 1H, J=10.9 Hz), 6.62 (dd, 1H, J1=14.9 Hz,J2=10.9 Hz), 6.82 (dd, 1H, J1=1.9 Hz, J2=7.6 Hz), 7.05 (m, 2H), 7.22 (t,1H, J=8.2 Hz), 7.30-7.38 (m, 3H).

EXAMPLE 66(4E,6Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol

a) (4E,6Z)-7-[3-Hydroxyphenyl]-3-ethylocta-4,6-dien-3-ol.

In a manner similar to Example 59(h), starting with 202 mg (0.56 mmol)of(Z)-7-[3-(tert-butyldimethylsilanyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol(obtained in Example 66(a), 138 mg (100%) of expected product arerecovered in the form of an oil.

b) Dimethyl4-[3-((1Z,3E)-5-Ethyl-5-hydroxy-1-methylhepta-1,3-dienyl)phenoxymethyl]phthalate

In a manner similar to Example 64(d), by reacting 138 mg (0.56 mmol) ofthe previous product with 196 mg (0.68 mmol) of dimethyl4-bromomethylphthalate, 152 mg (60%) of expected product are obtained inthe form of an oil.

c)(4E,6Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol.

In a manner similar to Example 53(e), by reacting 106 mg (0.23 mmol) ofdimethyl4-[3-((1Z,3E)-5-ethyl-5-hydroxy-1-methylhepta-1,3-dienyl)phenoxymethyl]phthalatewith 20 mg (0.94 mmol) of lithium borohydride, a colourless oil isobtained (m=50 mg; Y=55%).

¹H NMR (CDCl₃): 0.80 (t, 6H, J=7.5 Hz), 1.49 (q, 4H, J=7.5 Hz), 2.10 (s,3H), 3.21 (bs, 1H), 4.73 (s, 4H), 5.10 (s, 2H), 5.61 (d, 1H, J=14.9 Hz),6.12 (d, 1H, J=10.9 Hz), 6.24 (dd, 1H, J1=14.9 Hz, J2=10.9 Hz),6.83-6.98 (m, 3H), 7.18-7.42 (m, 4H).

EXAMPLE 677-[4-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol

In a manner similar to Example 53(e), by reacting 607 mg (1.33 mmol) ofdimethyl 4-[4-(5-ethyl-5-hydroxy-1-methylheptyl)phenoxymethyl]phthalate(prepared in a manner similar to Examples 64(a-d)) with 116 mg (5.32mmol) of lithium borohydride, a colourless oil is obtained (m=421 mg;Y=79%).

¹H NMR (CDCl₃): 0.73 (t, 6H, J=7.5 Hz), 1.09-1.47 (m, 13H), 2.56 (m,1H), 3.2 (bs, 1H), 4.62 (s, 4H), 4.94 (s, 2H), 6.80 (d, 2H, J=8.6 Hz),7.01 (d, 2H, J=8.6 Hz), 7.24-7.30 (m, 3H).

EXAMPLE 68(4E,6E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol

In a manner similar to Example 53(e), by reacting 122 mg (0.26 mmol) ofdimethyl4-[3-((1E,3E)-5-ethyl-5-hydroxy-1-ethylhepta-1,3-dienyl)phenoxymethyl]phthalate(prepared in a manner similar to Examples 65(a-c)) with 17 mg (0.78mmol) of lithium borohydride, a colourless oil is obtained (m=91 mg;Y=85%).

¹H NMR (CDCl₃): 0.81 (t, 6H, J=7.6 Hz), 0.96 (t, 3H, J=7.5 Hz), 1.52 (q,4H, J=7.6 Hz), 2.56 (q, 2H, J=7.5 Hz), 3.21 (bs, 2H), 4.57 (s, 2H), 4.58(s, 2H), 4.95 (s, 2H), 5.67 (d, 1H, J=15.1 Hz), 6.25 (d, 1H, J=11 Hz),6.53 (dd, 1H, J′=15.1 Hz, J2=11 Hz), 6.75 (dd, 1H, J1=1.7 Hz, J2=8.0Hz), 6.94-6.96 (m, 2H), 7.14 (t, 1H, J=8.1 Hz), 7.26-7.30 (m, 3H).

EXAMPLE 69(4E,6Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol

In a manner similar to Example 53(e), by reacting 72 mg (0.15 mmol) ofdimethyl4-[3-((1Z,3E)-5-ethyl-5-hydroxy-1-ethylhepta-1,3-dienyl)phenoxymethyl]phthalate(prepared in a manner similar to Examples 66(a-b)) with 10 mg (0.46mmol) of lithium borohydride, a colourless oil is obtained (m=62 mg;Y=100%).

¹H NMR (CDCl₃): 0.80 (t, 6H, J=7.6 Hz), 0.99 (t, 3H, J=7.5 Hz), 1.48 (q,4H, J=7.6 Hz), 2.41 (q, 2H, J=7.5 Hz), 3.71 (bs, 2H), 4.64 (s, 4H), 5.06(s, 2H), 5.63 (d, 1H, J=14.7 Hz), 6.08 (d, 1H, J=10.8 Hz), 6.19 (dd, 1H,J1=14.7 Hz, J2=10.8 Hz), 6.78-6.88 (m, 3H), 7.23 (t, 1H, J=8.2 Hz),7.29-7.37 (m, 3H).

EXAMPLE 70(E)-6-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylhept-3-en-2-ol

a) Ethyl 3-[3-(tert-Butyldimethylsilanyloxy)phenyl]-butyrate.

3 g (12 mmol) of 3-(tert-butyldimethylsilanyloxy)acetophenone in 20 mlare added dropwise to a solution, at 0° C., of 5 g (26.4 mmol) of ethyldiethylphosphonoacetate and 24 mmol of lithium diisopropylamide in 100ml of THF. The reaction medium is stirred for 15 hours at roomtemperature and then treated with an ammonium chloride solution andextracted with ethyl acetate. The organic phase is dried and thenconcentrated under reduced pressure. The residue obtained is thendissolved in 100 ml of ethyl acetate. The mixture is degassed with anargon stream and then 300 mg of 5% Pd/C are added. The assembly is thenequipped with a hydrogen flask (1 bar), and the reaction medium isstirred for 4 hours. After filtration and concentration, the residue ispurified by chromatography on a silica column. A colourless oil isobtained (m=3.15 g; Y=82%).

b) Methyl (E)-5-[3-(tert-Butyldimethylsilanyloxy)phenyl]hex-2-enoate

3.15 g (9.8 mmol) of ethyl3-[3-(tert-butyldimethylsilanyloxy)phenyl]butyrate are dissolved in 150ml of anhydrous ethyl ether. The mixture is cooled to 0° C. and thenlithium aluminium hydride (1.12 g, 29.4 mmol) is added in 4 equalportions. The reaction medium is heated under reflux for 4 h, and thenbrought to room temperature. After treating with 1.12 ml of water, 1.12ml of a 15% NaOH solution and then 3.4 ml of water, the medium isstirred for 1 h and then filtered. The filtrate is concentrated underreduced pressure. The residue obtained is then dissolved in 50 ml ofdichloromethane.

In a 500 ml round-bottomed flask, 2.28 g of oxalyl chloride (18 mmol)are dissolved in 100 ml of dichloromethane and the mixture is cooled to−78° C. 2.6 ml (36 mmol) of DMSO in 10 ml of dichloromethane are thenadded, and then the mixture is stirred for 15 minutes at −78° C. Thesolution of the alcohol obtained above is then slowly added by means ofa small tube and then the reaction medium is again stirred for 30minutes. 10 ml (72 mmol) of triethylamine are then added and thereaction medium is brought to room temperature. After stirring for 1hour, the medium is treated with a saturated ammonium chloride solutionand extracted with ethyl ether. The organic phase is rinsed with waterand then dried and concentrated under reduced pressure. The aldehydeobtained is immediately used as it is.

The residue is dissolved in 120 ml of anhydrous THF and then 6.4 g (19mmol) of methyl (triphenylphosphanylidene)acetate are added. Thereaction mixture is stirred for 12 hours under reflux and is thentreated with a saturated ammonium chloride solution and extracted withethyl acetate. After purification by chromatography on a silica column,a yellow oil is obtained (m=2.67 g; Y=82%).

c) 3-((E)-5-Hydroxy-1,5-dimethylhex-3-enyl)phenol.

800 mg (2.4 mmol) of methyl(E)-5-[3-(tert-butyldimethylsilanyloxy)phenyl]hex-2-enoate are dissolvedin 50 ml of anhydrous THF. The mixture is cooled to 0° C. and then 4.5ml (7.2 mmol) of a 1.6M solution of methyllithium are added dropwise.The reaction medium is stirred for 2 hours at 0° C. and is then treatedwith a saturated ammonium chloride solution and extracted with ethylacetate. After drying and concentrating the organic phase under reducedpressure, the residue is purified by chromatography on a silica column.The alcohol obtained (600 mg; 1.8 mmol) is then dissolved in 10 ml ofTHF, and 2 ml (2 mmol) of a tetrabutylammonium fluoride solution (1M inTHF) are added. After 15 min, the reaction medium is concentrated underreduced pressure and the residue is purified by chromatography on asilica column. A yellow oil is obtained (m=358 mg; Y=68%).

d)(E)-6-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylhept-3-en-2-ol.

In a manner similar to Example 53(e), by reacting 517 mg (1.2 mmol) ofdimethyl4-[3-((E)-5-hydroxy-1,5-dimethylhex-3-enyl)phenoxymethyl]phthalate(prepared by reacting the previous product with dimethyl4-bromomethylphthalate, in a manner similar to Example 64(d)) with 80 mg(3.6 mmol) of lithium borohydride, a colourless oil is obtained (m=430mg; Y=97%).

¹H NMR (CDCl₃): 1.18 (s, 6H), 1.22 (d, 3H, J=3.7 Hz), 2.19-2.25 (m, 2H),2.69 (m, 1H), 4.55 (s, 2H), 4.56 (s, 2H), 4.97 (s, 2H), 5.43-5.46 (m,2H), 6.71-6.77 (m, 3H), 7.14 (t, 1H, J=7.8 Hz), 7.28-7.34 (m, 3H).

EXAMPLE 71(E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyloct-4-en-3-ol

In a manner similar to Example 53(e), by treating 63 mg (0.14 mmol) ofdimethyl4-[3-((E)-5-ethyl-5-hydroxy-1-methylhept-3-enyl)phenoxymethyl]phthalate(prepared in a manner similar to Example 70) with 10 mg (0.4 mmol) oflithium borohydride, a colourless oil is obtained (m=54 mg; Y=97%).

¹H NMR (CDCl₃): 0.70 (t, 3H, J=7.5 Hz), 0.73 (t, 3H, J=7.5 Hz), 1.25 (d,3H, J=3.7 Hz), 1.42 (m, 4H), 2.29 (t, 2H, J=7 Hz), 2.74 (m, 1H), 3.8(bs, 2H), 4.65 (s, 2H), 4.66 (s, 2H), 5.03 (s, 2H), 5.23-5.47 (m, 2H),6.74-6.78 (m, 3H), 7.17 (t, 1H, J=7.8 Hz), 7.30-7.38 (m, 3H).

EXAMPLE 72(E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol

a) Methyl 5-(3-Hydroxyphenyl)hex-4-enoate.

3.54 g of (3-carboxypropyl)triphenylphosphonium bromide (8.25 mmol) areadded to a sodium hydride solution (400 mg, 16.5 mmol) in 15 ml of DMSO.After 20 min, 1 g (5.5 mmol) of 1-(3-methoxymethoxyphenyl)ethanone in 5ml of DMSO are added by means of a small tube, and then the reactionmedium is stirred for 15 hours at room temperature. After treating with50 ml of water and 50 ml of toluene, the aqueous phase is separated andthen acidified with a 2M solution of HCl and finally extracted withethyl acetate. The organic phase is then dried and then concentratedunder reduced pressure. The residue obtained is then dissolved in 50 mlof ethanol and then the mixture is heated to reflux temperature afteraddition of 1 ml of sulphuric acid. After stirring for 2 hours, thereaction medium is poured into a water/dichloromethane mixture and thephases are separated. The organic phase is dried and concentrated underreduced pressure and the residue is purified by chromatography on asilica column. A colourless oil is obtained (m=260 mg; Y=22%).

b) 3-Ethyl-7-(3-hydroxyphenyl)oct-6-en-3-ol.

In a manner similar to Example 65(a), starting with 443 mg (2 mmol) ofthe previous product, 237 mg (48%) of(Z)-3-ethyl-7-(3-hydroxyphenyl)oct-6-en-3-ol and 112 mg (23%) of(E)-3-ethyl-7-(3-hydroxyphenyl)-oct-6-en-3-ol are obtained.

c) Dimethyl4-[3-((E)-5-Ethyl-5-hydroxy-1-methylhept-1-enyl)phenoxymethyl]phthalate.

In a manner similar to Example 64(d), by reacting 112 mg (0.39 mmol) of(E)-3-ethyl-7-(3-hydroxyphenyl)oct-6-en-3-ol with 145 mg (0.51 mmol) ofdimethyl 4-bromomethylphthalate, 131 mg (74%) of expected product areobtained in the form of an oil.

d)(E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-3-ethyloct-6-en-3-ol.

In a manner similar to Example 53(e), by reacting 131 mg (0.29 mmol) ofdimethyl4-[3-((E)-5-ethyl-5-hydroxy-1-methylhept-1-enyl)phenoxymethyl]phthalatewith 25 mg (1.15 mmol) of lithium borohydride, a colourless oil isobtained (m=89 mg; Y=78%).

¹H NMR (CDCl₃): 0.88 (t, 6H, J=7.5 Hz), 1.45-1.57 (m, 4H), 1.98 (s, 3H),2.03-2.20 (m, 2H), 3.78 (bs, 2H), 4.63 (s, 2H), 4.64 (s, 2H), 5.02 (s,2H), 5.76 (t, 1H, 7.1 Hz), 6.79 (m, 1H), 6.95-6.98 (m, 2H) 7.15-7.36 (m,4H).

EXAMPLE 73(Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol

a) Dimethyl4-[3-((Z)-5-Ethyl-5-hydroxy-1-methylhept-1-enyl)phenoxymethyl]phthalate.

In a manner similar to Example 64(d), by reacting 234 mg (0.95 mmol) of(Z)-3-ethyl-7-(3-hydroxyphenyl)oct-6-en-3-ol with 356 mg (1.24 mmol) ofdimethyl 4-bromomethylphthalate, .398 mg (92%) of expected product areobtained in the form of an oil.

b)(Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-3-ethyloct-6-en-3-ol.

In a manner similar to Example 53(e), by reacting 431 mg (0.95 mmol) ofdimethyl4-[3-((Z)-5-ethyl-5-hydroxy-1-methylhept-1-enyl)phenoxymethyl]-phthalatewith 83 mg (3.8 mmol) of lithium borohydride, a colourless oil isobtained (m=286 mg; Y=76%).

¹H NMR (CDCl₃): 0.74 (t, 6H, J=7.5 Hz), 1.22-1.42 (m, 6H), 1.84-1.94 (m,2H), 1.99 (s, 3H), 4 (bs, 2H), 4.59 (s, 2H), 4.60 (s, 2H), 5.01 (s, 2H),5.41 (t, 1H, 7.1 Hz), 6.75-6.84 (m, 3H), 7.17-7.35 (m, 4H).

EXAMPLE 74(E)-8-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol

In a manner similar to Example 53(e), by reacting 204 mg (0.46 mmol) ofdimethyl4-[3-((E)-7-hydroxy-1,7-dimethyloct-1-enyl)phenoxymethyl]-phthalate(prepared in a manner similar to Examples 72(a-c)) with 30 mg (1.4 mmol)of lithium borohydride, a colourless oil is obtained (m=146 mg; Y=82%).

¹H NMR (CDCl₃): 1.18 (s, 6H), 1.18-1.51 (m, 6H), 1.99 (s, 3H), 2.16-2.22(m, 2H), 3.7 (bs, 2H), 4.61 (s, 2H), 4.62 (s, 2H), 5.01 (s, 2H), 5.76(t, 1H), 6.77-6.81 (m, 1H), 6.96-6.99 (m, 2H), 7.15-7.35 (m, 4H).

EXAMPLE 75(Z)-8-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol

In a manner similar to Example 53(e), by reacting 790 mg (1.8 mmol) ofdimethyl4-[3-((Z)-7-hydroxy-1,7-dimethyloct-1-enyl)phenoxymethyl]phthalate(prepared in a manner similar to Example 73(a)) with 118 mg (5.4 mmol)of lithium borohydride, a colourless oil is obtained (m=621 mg; Y=86%).

¹H NMR (CDCl₃): 1.11 (s, 6H), 1.17-1.36 (m, 6H), 1.98 (s, 3H), 1.90-1.99(m, 2H), 4.56 (s, 2H), 4.57 (s, 2H) 4.98 (s, 2H), 5.41 (t, 1H),6.75-6.82 (m, 3H), 7.17-7.35 (m, 4H).

EXAMPLE 76(E)-9-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol

In a manner similar to Example 53(e), by reacting 397 mg (0.85 mmol) ofdimethyl4-[3-((E)-7-ethyl-7-hydroxy-1-methylnon-1-enyl)phenoxymethyl]phthalate(prepared in a manner similar to Examples 72(a-c)) with 55 mg (2.5 mmol)of lithium borohydride, a colourless oil is obtained (m=323 mg; Y=92%).

¹H NMR (CDCl₃): 0.78 (t, 6H, J=7.5 Hz), 1.20-1.42 (m, 10H), 1.99 (s,3H), 1.91-1.99 (m, 2H), 4.38 (bs, 2H), 4.57 (s, 2H), 4.58 (s, 2H), 4.99(s, 2H), 5.42 (t, 1H, J=6.9 Hz), 6.76-6.82 (m, 3H), 7.17-7.35 (m, 4H).

EXAMPLE 77(Z)-9-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol

In a manner similar to Example 53(e), by reacting 1.21 g (2.58 mmol) ofdimethyl4-(3-((Z)-7-ethyl-7-hydroxy-1-methylnon-1-enyl)phenoxymethyl]-phthalate(prepared in a manner similar to Example 73(a)) with 170 mg (7.76 mmol)of lithium borohydride, a colourless oil is obtained (m=865 mg; Y=81%).

¹H NMR (CDCl₃): 0.84 (t, 6H, J=7.5 Hz), 1.30-1.48 (m, 10H), 1.99 (s,3H), 2.16-2.23 (m, 2H), 4.1 (bs, 2H), 4.60 (s, 2H), 4.61 (s, 2H), 5.00(s, 2H), 5.76 (t, 1H, J=6.2 Hz), 6.76-6.82 (m, 2H), 6.95-6.99 (m, 1H),7.15-7.35 (m, 4H).

EXAMPLE 788-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methyl-2-nonanol

a) 3-(7-Hydroxy-1,7-dimethyloctyl)phenol.

125 mg (0.32 mmol) of(Z)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol(obtained in Example 75) are dissolved in 25 ml of methanol. NaNO₂ (620mg, 9 mmol) is then added to the solution and then 50 mg of 5% Pd/C. Theassembly is then equipped with a hydrogen flask (1 bar) and the reactionmedium is stirred for 5 hours. The reaction medium is then filtered andthen the filtrate is added to 50 ml of water and then extracted withdichloromethane. The organic phase is then dried and concentrated underreduced pressure. The residue is purified by chromatography on a silicacolumn (ethyl acetate 20-heptane 80) and then ethyl acetate 50-heptate50). A colourless oil is obtained (m=50 mg; Y=95%).

b) 8-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2-methyl-2-nonanol.

In a manner similar to Example 53(e), by reacting 97 mg (0.21 mmol) ofdimethyl 4-[3-(7-hydroxy-1,7-dimethyloctyl)phenoxymethyl]phthalate(prepared from the previous product in a manner similar to Example 64(d)with 14 mg (0.63 mmol) of lithium borohydride, a colourless oil isobtained (m=83 mg; Y=99%).

¹H NMR (CDCl₃): 1.09 (s, 6H), 1.10-1.18 (m, 9H), 1.26-1.31 (m, 2H),1.40-1.48 (m, 2H), 2.51-2.58 (m, 1H), 3.0 (bs, 2H), 4.60 (s, 2H), 4.61(s, 2H), 4.96 (s, 2H), 6.68-6.73 (m, 3H), 7.08-7.32 (m, 4H).

EXAMPLE 799-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyldecan-3-ol

In a manner similar to Example 78, starting with(Z)-9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol(prepared in Example 77),9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldecan-3-ol isobtained in the form of an oil.

¹H NMR (CDCl₃): 0.74 (t, 6H, J=7.6 Hz), 1.12-1.38 (m, 15H), 1.44-1.47(m, 2H), 2.50-2.60 (m, 1H), 4.70 (bs, 2H), 4.56 (s, 2H), 4.57 (s, 2H),4.93 (s, 2H), 6.66-6.72 (m, 3H), 7.07-7.29 (m, 4H).

EXAMPLE 80(E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-4-yn-3-ol

a) 1-Methoxymethoxy-3-((E)-1-methylbut-1-en-3-ynyl)benzene.

2.47 g (9.9 mmol) of diethyl (3-trimethylsilanylprop-2-ynyl)phosphonateare dissolved in 20 ml of anhydrous THF and then the solution is cooledto −78° C. A solution of 1.94 g (10.6 mmol) of lithiumbis-trimethylsilylamide in 10 ml of THF is added dropwise. Afterstirring for 30 minutes at −78° C., 1.2 g (6.6 mmol) of3-methoxymethoxyacetophenone in 10 ml of THF are added dropwise by meansof a small tube. The reaction medium is stirred for 30 minutes at −78°C. and is then brought to room temperature and stirred for 24 hours. Thereaction medium is then treated with water and then extracted with ethylacetate. The organic phase is dried and then concentrated under reducedpressure and then the residue is filtered on a silica pad. The residueobtained is then dissolved in 25 ml of THF and 8 ml (8 mmol) of atetrabutylammonium fluoride solution (1M in THF) are added. After 15minutes at room temperature, the reaction medium is concentrated and theresidue purified by chromatography on a silica column (ethyl acetate5-heptane 95). A yellow oil is obtained (m=1.11 g; Y=83%).

b) Ethyl (E)-5-(3-Methoxymethoxyphenyl)hex-4-en-2-ynoate

764 mg (3.78 mmol) of1-methoxymethoxy-3-((E)-1-methylbut-1-en-3-ynyl)benzene are dissolved in20 ml of anhydrous THF and the solution is cooled to −78° C. 1.8 ml (4.5mmol) of a 2.5M butyllithium solution are then added dropwise and thereaction medium is stirred for 30 minutes at this temperature. 0.43 ml(4.5 mmol) of ethyl chloroformate are then added dropwise and then thereaction medium is brought to room temperature and stirred for 2 hours.After treating with a saturated ammonium chloride solution andextracting with ethyl acetate, the organic phase is dried and thenconcentrated under reduced pressure. After purification bychromatography on a silica column (ethyl acetate 10-heptane 90), ayellow oil is obtained (m=836 mg; Y=81%).

c) Ethyl (E)-5-(3-Hydroxyphenyl)hex-4-en-2-ynoate.

800 mg (2.9 mmol) of ethyl(E)-5-(3-methoxymethoxyphenyl)hex-4-en-2-ynoate are dissolved in 50 mlof ethanol and then 1 ml of sulphuric acid is added to the solution. Thereaction medium is stirred for 14 h, treated with water and extractedwith dichloromethane. The organic phase is dried, concentrated underreduced pressure and the residue is purified by chromatography (ethylacetate 10-heptane 90) and then (ethyl acetate 20-heptane 80). A yellowoil is obtained (m=676 mg; Y=100%).

d)(E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-3-ethyloct-6-en-4-yn-3-ol.

In a manner similar to Example 53(e), by reacting 390 mg (0.87 mmol) ofdimethyl4-[3-((E)-5-ethyl-5-hydroxy-1-methylhept-1-en-3-ynyl)phenoxymethyl]phthalate(prepared from the previous product in a manner similar to Example64(d)) with 56 mg (2.6 mmol) of lithium borohydride, a colourless oil isobtained (m=248 mg; Y=72%).

¹H NMR (CDCl₃): 1.09 (t, 6H, J=7.6 Hz), 1.70-1.79 (m, 4H), 2.27 (d, 3H,J=1 Hz), 3.14 (bs, 2H), 4.72 (s, 2H), 4.73 (s, 2H), 5.05 (s, 2H), 5.89(d, 1H, J=1 HZ), 6.86-6.91 (m, 1H), 7.01-7.05 (m, 2H), 7.21-7.41 (m,4H).

EXAMPLE 81(3E,5E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2,7-dimethylocta-3,5-dien-2-ol

a) Methyl 2-[3-(tert-Butyldimethylsilanyloxy)phenyl]-2-methylpropionate.

2 g (7.1 mmol) of methyl [3-(tert-butyldimethylsilanyloxy)phenyl]acetateare added to a lithium diisopropylamide solution (20.6 mmol) in 100 mlof THF at 0° C. and then the medium is stirred for 30 minutes. 2.2 ml(35.5 mmol) of methyl iodide are then added dropwise and the reactionmedium is brought to room temperature and stirred for 18 hours. Thereaction medium is treated with a saturated ammonium chloride solutionand then extracted with ethyl ether. The residue obtained is subjectedto the same conditions described above. After 12 h, the reaction mediumis treated with a saturated ammonium chloride solution and thenextracted with ethyl ether. The organic phase is dried and thenconcentrated under reduced pressure. The residue obtained is thenpurified by chromatography on a silica column in order to obtain acolourless oil (m=1.526 g; Y=70%).

b) 2-[3-(tert-Butyldimethylsilanyloxy)phenyl]-2-methylpropionaldehyde.

1.53 g (4.9 mmol) of methyl2-[3-(tert-butyldimethylsilanyloxy)phenyl]-2-methylpropionate aredissolved in 100 ml of anhydrous ethyl ether. The mixture is cooled to0° C. and then lithium aluminium hydride (760 mg, 20 mmol) is added in 2equal portions. The reaction medium is heated under reflux for 4 h andis then brought to room temperature. After treating with 0.76 ml ofwater, 0.76 ml of a 15% NaOH solution and then 2.3 ml of water, themedium is stirred for 1 h and then filtered. The filtrate isconcentrated under reduced pressure. The residue obtained is thendissolved in 20 ml of dichloromethane.

In a 100 ml round-bottomed flask, 0.95 g of oxalyl chloride (7.5 mmol)is dissolved in 20 ml of dichloromethane and the mixture is cooled to−78° C. 1.06 ml (15 mmol) of DMSO in 5 ml of dichloromethane are thenadded and then the mixture is stirred for 15 minutes at −78° C. Thesolution of the alcohol previously obtained is then slowly added bymeans of a small tube and then the reaction medium is again stirred for30 minutes. 4.2 ml (30 mmol) of triethylamine are then added and thereaction medium is brought to room temperature. After stirring for 1hour, the medium is treated with a saturated ammonium chloride solutionand extracted with ethyl ether. The organic phase is rinsed with waterand then dried and concentrated under reduced pressure. The residue ispurified by chromatography on a silica column (ethyl acetate 5-heptane95). A colourless oil is obtained (m=1.08 g; Y=75%).

c) Ethyl(2E,4E)-6-[3-(tert-Butyldimethylsilanyloxy)phenyl]-6-methylhepta-2,4-dienoate.

1.7 ml (7.5 mmol) of ethyl 4-diethylphosphonocrotonate are dissolved in50 ml of THF and then the mixture is cooled to 0 C. 3.4 ml (6.8 mmol) ofa 2M solution of lithium diisopropylamide are added dropwise and thereaction medium is stirred for 30 minutes. 1 g (3.4 mmol) of2-[3-(tert-butyldimethylsilanyloxy)-phenyl]-2-methylpropionaldehyde in10 ml of THF is then slowly added by means of a small tube. The reactionmedium is brought to room temperature and is then stirred for 4 hours.After treating with a saturated ammonium chloride solution, the organicphase is dried and concentrated under reduced pressure. The residue isfiltered on a silica pad. A yellow oil is obtained (m=1.26 g; Y=99%).

c) Ethyl (2E,4E)-6-[3-Hydroxyphenyl]-6-methylhepta-2,4-dienoate.

In a manner similar to Example 59(h), starting with 568 mg (1.5 mmol) ofthe previous product, 284 mg (75%) of expected product are obtained inthe form of an oil.

d)(3E,5E)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-2,7-dimethylocta-3,5-dien-2-ol.

In a manner similar to Example 53(e), by reacting 360 mg (0.8 mmol) ofdimethyl4-[3-((2E,4E)-6-hydroxy-1,1,6-trimethylhepta-2,4-dienyl)phenoxymethyl]phthalate(prepared from the previous product in a manner similar to Example64(d)) with 70 mg (3.2 mmol) of lithium borohydride, a colourless oil isobtained (m=220 mg; Y=70%).

¹H NMR (CDCl₃): 1.33 (s, 6H), 1.40 (s, 6H), 2.27 (bs, 2H), 4.35 (bs,1H), 4.71 (s, 4H), 5.04 (s, 2H), 5.75-10 5.87 (m, 2H), 6.02 (dd, 1H,J₁=15.3 Hz, J₂=10 Hz), 6.22 (dd, 1H, J₁=15.3 Hz, J₂=10 Hz), 6.78 (dd,1H, J₁=1.6 Hz, J₂=8.2 Hz), 6.92-6.95 (m, 2H), 7.21 (t, 1H, J=8.2 Hz),7.37 (s, 2H), 7.44 (s, 1H).

EXAMPLE 82(4E,6E)-7-[3-(3,4-bis-Hydroxymethylphenoxy-methyl)phenyl]-3-ethylocta-4,6-dien-3-ol

a)(4E,6E)-7-{3-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}-3-ethylocta-4,6-dien-3-ol.

Ethyl5-{3-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}hexa-2,4-dienoate(prepared in Example 6(i)) (800 mg, 1.3 mmol) is dissolved in 10 ml ofTHF and cooled to 0° C. 9 ml (13 mmol) of a 1.5M solution ofethyllithium are slowly added and then the stirring is continued for 3hours. After treating with a saturated ammonium chloride solution andthen extracting with ethyl ether, the organic phases are combined, driedand then concentrated under reduced pressure. After purification bychromatography on a silica column (heptane eluent), the expected productis obtained in the form of a colourless oil (m=410 mg, Y=50%).

b)(4E,6E)-7-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-3-ethylocta-4,6-dien-3-ol.

In a manner similar to Example 57(c) by reacting 520 mg (0.83 mmol) of(4E,6E)-7-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]-phenyl}-3-ethylocta-4,6-dien-3-olwith 2.5 ml of a tetrabutylammonium fluoride solution (1N in THF), acolourless oil is obtained (m=164 mg; Y=50%).

¹H NMR (CDCl₃): 0.90 (t, 6H, J=7.4 Hz), 1.57 (q, 4H, J=7.4 Hz), 2.19 (s,3H), 2.6 (bs, 2H), 4.69 (s, 2H), 4.71 (s, 2H), 5.08 (s, 2H), 5.79 (d,1H, J=14.9 Hz), 6.49 (d, 1H, J=10.9 Hz), 6.65 (dd, 1H, J₁=14.9 Hz,J₂=10.9 Hz), 6.90 (dd, 1H, J₁=2.6 Hz, J₂=8.2 Hz), 7.03 (m, 1H),7.25-7.50 (m, 5H).

EXAMPLE 83(3E,5E)-6-[3-(3,4-bis-Hydroxymethylphenoxy-methyl)phenyl]-2-methylhepta-3,5-dien-2-ol

a)(3E,5E)-6-{3-[3,4-bis(tert-Butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}-2-methylhepta-3,5-dien-2-ol.

Ethyl5-{3-[3,4-bis(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]phenyl}hexa-2,4-dienoate(prepared in Example 6(i)) (4.17 mg, 0.7 mmol) is dissolved in 6 ml ofTHF and cooled to 0° C. 2 ml (2.8 mmol) of a 1.4M solution ofmethyllithium are slowly added and then the stirring is continued for 3hours. After treating with a saturated ammonium chloride solution andthen extracting with ethyl ether, the organic phases are combined, driedand then concentrated under reduced pressure. After purification bychromatography on a silica column (heptane eluent), the expected productis obtained in the form of a colourless oil (m=120 mg, Y=30%).

b)(3E,5E)-6-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-2-methylhepta-3,5-dien-2-ol.

In a manner similar to Example 57(c), by reacting 120 mg (0.2 mmol) of(3E,5E)-6-{3-[3,4-bis-(tert-butyldimethylsilanyloxymethyl)phenoxymethyl]-phenyl}-2-methylhepta-3,5-dien-2-olwith 0.6 ml of a tetrabutylammonium fluoride solution (1N in THF), acolourless oil is obtained (m=30 mg; Y=41%).

¹H NMR (CDCl₃): 1.39 (s., 6H), 2.19 (s, 3H), 2.9 (bs, 2H), 4.67 (s, 2H),4.69 (s, 2H), 5.07 (s, 2H), 5.96 (d, 1H, J=15 Hz), 6.44 (d, 1H, J=10.9Hz), 6,64 (dd, 1H, J₁=15 Hz, J₂=10.9 Hz), 6.89 (dd, 1H, J₁=2.7 Hz,J₂=8.2 Hz), 7.02 (m, 1H), 7.24-7.49 (m, 5H).

EXAMPLE 84(Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-3-ethylnon-6-en-3-ol

a) Ethyl (Z)-5-(3-Hydroxyphenyl)hex-4-enoate.

5.3 g (12.4 mmol) of (3-carboxypropyl)triphenylphosphonium bromide aredried under vacuum for 1 h by heating to 130° C. and then brought toroom temperature and dissolved in 100 ml of anhydrous THF. 2.75 g (25mmol) of potassium tert-butoxide in 50 ml of THF are then slowly addedand then the orange-red mixture is stirred for 15 minutes. A solution of1.2 g (6.2 mmol) of 1-(3-methoxymethoxyphenyl)-1-propanone in 50 ml ofTHF is then added dropwise and the reaction medium is stirred for 15hours. After treating with a saturated ammonium chloride solution andextracting with ethyl acetate and then drying and evaporating thesolvents of the organic phase, the residue is then dissolved in 50 ml ofethanol, and then 1 ml of sulphuric acid is added. The reaction mediumis heated to reflux temperature and stirred for 2 hours. After treatingwith water, the medium is extracted with ethyl acetate and then theorganic phases are combined, dried and concentrated under reducedpressure. The residue is purified by chromatography on a silica column(eluent heptane 95-ethyl acetate 5) in order to obtain a yellow oil(m=670 mg; Y=43%).

b) Ethyl(Z)-5-{3-[3,4-bis(1-Phenylmethanoyloxymethyl)]phenyl}hept-4-enoate.

670 mg (2.7 mmol) of ethyl (Z)-5-(3-hydroxyphenyl)hex-4-enoate, 1.42 g(3.2 mmol) of (3,4-bis-benzoyloxymethyl)benzyl bromide and 450 mg (3.2mmol) of potassium carbonate are dissolved in 20 ml of 2-butanone. Themixture is heated under reflux (80° C.) and then stirred for 4 h. Aftercooling, the reaction medium is filtered and then concentrated underreduced pressure. The residue is purified by chromatography on a silicacolumn (m=1.18 g; Y=73%).

c)(Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylnon-6-en-3-ol.

800 mg (1.32 mmol) of ethyl(Z)-5-{3-[3,4-bis(1-phenylmethanoyloxymethyl)]phenyl}hept-4-enoate aredissolved in 30 ml of anhydrous THF and then the mixture is cooled to 0°C. 4.4 ml (13 mmol) of a 3M solution of ethylmagnesium bromide are thenadded and then the reaction medium is brought to room temperature andstirred for 1 h. After treating with a saturated ammonium chloridesolution and then extracting with ethyl acetate, the organic phases arecombined, dried and concentrated under reduced pressure. Afterpurification by chromatography on a silica column, a colourless oil isobtained (m=309 mg; Y=57%).

¹H NMR (CDCl₃): 0.74 (t, 6H, J=7.5 Hz), 0.95 (t, 3H, 7.4 Hz), 1.25-1.40(m, 6H), 1.78-1.90 (m, 2H), 2.29 (q, 2H, J=7.4 Hz), 3.5 (bs, 2H), 4.68(s, 4H), 5.07 (s, 2H), 5.38 (t, 1H, J=7.3 Hz), 6.70-6.85 (m, 2H),7.18-7.39 (m, 5H).

EXAMPLE 85(Z)-6-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-2-methyloct-5-en-2-ol

In a manner similar to Example 84(c), by reacting 380 mg (0.63 mmol) ofethyl(Z)-5-{3-[3,4-bis-(1-phenylmethanoyloxymethyl)]phenyl}hept-4-enoate(prepared in a manner similar to Examples 84(a-b)) with 2.1 ml (6.3mmol) of a 3.0M solution of methylmagnesium bromide, a colourless oil isobtained (m=178 mg; Y=74%).

¹H NMR (CDCl₃): 0.87 (t, 3H, 7.4 Hz) 0.98 (s, 6H), 1.32-1.39 (m, 2H),1.78-1.85 (m, 2H), 2.17-2.24 (m, 2H), 3.7 (bs, 2H), 4.58 (s, 2H), 4.60(s, 2H), 4.99 (s, 2H), 5.28 (t, 1H), 6.63-6.78 (m, 2H), 7.11-7.30 (m,5H).

EXAMPLE 86(Z)-7-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-3-ethyldec-6-en-3-ol

In a manner similar to Example 84(c), by reacting 1 g (1.6 mmol) ofethyl (Z)-5-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]oct-4-enoate(prepared in a manner similar to Examples 84(a-b)) with 5.4 ml (16 mmol)of a 3.0M solution of ethylmagnesium bromide, a colourless oil isobtained (m=480 mg; Y=70%).

¹H NMR (CDCl₃): 0.70 (t, 6H, J=7.5 Hz), 0.81-0.91 (m, 5H), 1.25-1.37 (m,6H), 1.45-1.54 (m, 2H), 1.70-1.90 (m, 2H), 2.40-2.45 (m, 2H), 3.5 (bs,1H), 3.69 (bs, 1H), 4.66 (s, 4H), 5.06 (s, 2H), 5.39 (t, 1H, J=7.3 Hz),6.70-6.85 (m, 2H), 7.18-7.39 (m, 5H).

EXAMPLE 87(Z)-6-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-2-methylnon-5-en-2-ol

In a manner similar to Example 84(c), by reacting 1 g (1.6 mmol) ofethyl (Z)-5-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]oct-4-enoate(prepared in a manner similar to Examples 84(a-b)) with 5.4 ml (16 mmol)of a 3.0M solution of methylmagnesium bromide, a colourless oil isobtained (m=516 mg; Y=81%).

¹H NMR (CDCl₃): 0.84 (t, 3H, J=7.4 Hz), 1.06 (s, 6H), 1.28-1.47 (m, 4H),1.84-1.90 (m, 2H), 2.26 (t, 2H, J=6.7 Hz), 3.5 (bs, 2H), 4.69 (s, 4H),5.08 (s, 2H), 5.38 (t, 1H), 6.70-6.85 (m, 2H), 7.18-7.40 (m, 5H).

EXAMPLE 88(Z)-8-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-3-ethylnon-7-en-3-ol

a) Ethyl 6-(3-Hydroxyphenyl)hept-5-enoate

21.6 g (48.7 mmol) of (4-carboxybutyl)triphenylphosphonium bromide aredried under vacuum for 1 h by heating to 130° C., and then brought toroom temperature and dissolved in 300 ml of anhydrous THF. 10.9 g (97mmol) of potassium tert-butoxide in 100 ml of THF are then slowly addedand then the orange-red mixture is stirred for 15 minutes. A solution of6.3 g (32.5 mmol) of 1-(3-methoxymethoxyphenyl)-1-ethanone in 50 ml ofTHF is then added dropwise and the reaction medium is stirred for 15hours. After treating with a saturated ammonium chloride solution andextracting with ethyl acetate and then drying and evaporating thesolvants of the organic phase, the residue is then dissolved in 50 ml ofethanol and then 1 ml of sulphuric acid is added. The reaction medium isheated to reflux temperature and stirred for 2 hours. After treatingwith water, the medium is extracted with ethyl acetate and then theorganic phases are combined, dried and concentrated under reducedpressure. The residue is purified by chromatography on a silica column(eluent heptane 80-ethyl acetate 20) in order to obtain 1 g (12%) ofethyl (Z)-6-(3-hydroxyphenyl)hept-5-enoate and 1.3 g (16%) of ethyl(E)-6-(3-hydroxyphenyl)hept-5-enoate.

b) Ethyl(Z)-6-{3-[3,4-bis(1-Phenylmethanoyloxymethyl)]phenyl}hept-5-enoate.

1 g (4 mmol) of ethyl (Z)-6-(3-hydroxyphenyl)hept-5-enoate is dissolvedin 20 ml of DMF and 180 mg of NaH (60% in oil) are added. The reactionmedium is stirred until the gaseous emission ceases and then a solutionof 1.9 g (4.4 mmol) of (3,4-bis-benzoyloxymethyl)benzyl bromide in 100ml of DMF is added. The mixture is stirred for 14 h, extracted betweenwater and ethyl acetate and separated after settling out. The organicphases are dried over magnesium sulphate and evaporated. The residueobtained is purified by chromatography on a silica column (heptane80-ethyl acetate 20) (m=2.2 g; Y=90%).

c)(Z)-8-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol.

In a manner similar to Example 84(c), by reacting 2.2 g (3.6 mmol) ofethyl(Z)-6-{3-[3,4-bis-(1-phenylmethanoyloxymethyl)]phenyl}hept-5-enoate with9.7 ml (29 mmol) of a 3M solution of ethylmagnesium bromide, acolourless oil is obtained (m=1.1 g; Y=74%).

¹H NMR (CDCl₃): 0.82 (t, 6H, J=7.5 Hz), 1.23-1.28 (m, 4H), 1.41 (q, 4H,J=7.5 Hz), 1.87-1.90 (m, 2H), 2.00 (s, 3H), 3.1 (bs, 2H), 4.75 (s, 2H),4.76 (s, 2H), 5.09 (s, 2H), 5.42 (t, 1H, J=5.9 Hz), 6.76-6.88 (m, 3H),7.22-7.43 (m, 4H).

EXAMPLE 89(E)-8-[3(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-3-ethylnon-7-en-3-ol

a) Dimethyl 4-Hydroxymethylphthalate.

1,2,4-Benzenetricarboxylic anhydride (50 g, 260 mmol) is dissolved in800 ml of anhydrous dioxane, at room temperature. BH₃.THF (260 mmol, 1eq.) is then added dropwise by means of a dropping funnel, over a periodof about 1 h 30 min. The stirring is maintained for 12 h and then thereaction medium is poured into a mixture containing 600 ml of asaturated NH₄Cl solution and 2 l of dichloromethane. After separating,the organic phase is dried and the solvents are evaporated under reducedpressure. The residue obtained is then dissolved in 1 l of methanol andheated to reflux temperature after addition of 5 ml of sulphuric acid.After refluxing for 18 h, the reaction medium is cooled to roomtemperature and directly poured into a water/ethyl ether mixture (1 l/2l). After separating, the aqueous phase is again extracted with twofractions of ethyl ether (about 700 ml) and then the organic phases arecombined and dried and then concentrated under reduced pressure. Atriester-diester/alcohol mixture is obtained with a yield of 80%,containing 65% of the desired product.

b) Dimethyl 4-(tert-Butyldimethylsilanyloxymethyl)phthalate.

The mixture obtained above, containing about 135 mmol of desiredproduct, is dissolved in 400 ml of anhydrous DMF.tert-Butyldimethylsilane chloride (22.5 g, 150 mmol) is then added in asingle portion. Next, a total of 13.5 g (195 mmol) of imidazole is addedin three portions (slight exothermicity). The reaction medium is stirredfor 36 hours and then concentrated under reduced pressure. The residueis then dissolved in 500 ml of ethyl ether and then filtered in order toremove the imidazole hydrochloride formed. The salt is rinsed with 2fractions of 150 ml of ethyl ether and then the organic phases are driedand concentrated under reduced pressure. The residue is then purified bychromatography: the first product collected (eluent AcOEt 10-heptane 90)is the desired dimethyl 4-(tert-butyldimethylsilanyloxymethyl)phthalate.Yield 87%, overall yield from the initial acid: 45%.

c)[5-(tert-Butyldimethylsilanyloxymethyl)-2-hydroxymethylphenyl]methanol.

The diester obtained above (75 g, 220 mmol) is dissolved in 1 l of ethylether and cooled to 0° C. under a positive nitrogen pressure., 4fractions of 5 g of LiAlH₄ (527 mmol) are added with care and then themixture is heated to 50° C. After stirring for 1 h 30 min, the reactionmedium is again cooled to 0° C. and then treated successively with 20 mlof water, 20 ml of 15% NaOH and then 60 ml of water. The reaction mediumis stirred for 30 minutes until the complete disappearance of the greyaluminium salts and their precipitation as white floccules are observed.The medium is then filtered and after rinsing the salts with threefractions of ethyl acetate (200 ml), the organic phases are combined,dried and concentrated under reduced pressure. The product obtainedrepresents a yield of 97%.

d) 2-Benzoyloxymethyl-4-(tert-butyldimethylsilanyloxymethyl)benzylBenzoate.

The crude diol obtained above (60 g, 212 mmol) is dissolved in 600 ml ofanhydrous THF and cooled to 0° C. 74 ml (530 mmol) of triethylamine arethen added, followed by 52 ml (448 mmol) of benzoyl chloride. DMAP (500mg) is then added in a single portion and the mixture is stirred for 30minutes at 0° C. and then for 12 hours at room temperature. The reactionmedium is then filtered in order to remove the precipitatedtriethylammonium salts, the salts are rinsed with two fractions of 200ml of ethyl acetate and then the mixture of the organic phases isconcentrated under reduced pressure, taken up in dichloromethane, rinsedwith a saturated NH₄Cl solution and finally with a fraction of water.After drying, the organic phase is concentrated under reduced pressure,giving a dark yellow residue which is used as it is for the next step.

e) 2-Benzoyloxymethyl-4-hydroxymethylbenzyl Benzoate.

The residue obtained above is dissolved in 600 ml of ethyl acetate and220 ml of a tetrabutylammonium fluoride solution (1M in THF) are addedin a single fraction. After stirring for 30 minutes at room temperature,the reaction medium is poured into a separating funnel containing 1 l ofsaturated NH₄Cl. After separating, the aqueous phase is again extractedwith 500 ml of ethyl acetate and then the organic phases are combined,dried and evaporated. The product is then purified by chromatography(ethyl acetate 30-heptane 70). A white solid is obtained (m.p.: 91-93°C.).

f) (3,4-bis-Benzoyloxymethyl)benzyl Bromide.

The above alcohol (65 g, 172 mmol) is dissolved in 350 ml ofdichloromethane and CBr₄ (67.7 g, 202 mmol) is added. The medium iscooled to 0° C. and then a solution of triphenylphosphine (53 g, 202mmol) in 250 ml of dichloromethane is added dropwise. The reactionmedium is then heated to room temperature and then stirred for 2 hours.The medium is then treated with 500 ml of water and then extracted withdichloromethane. After drying and concentrating the organic phases, theproduct is purified by chromatography (eluent CH₂Cl₂/EtOAc) in order toobtain a white solid (m.p.: 83° C.) with a yield of 93%.

g) Ethyl(E)-6-{3-[3,4-bis(1-Phenylmethanoyloxymethyl)]phenyl}hept-5-enoate

500 mg (2 mmol) of ethyl (E)-6-(3-hydroxyphenyl)hept-5-enoate (obtainedin Example 88(a)) are dissolved in 20 ml of DMF and 90 mg of NaH (60% inoil) are added. The reaction medium is stirred until the gaseousemission ceases and then a solution of 950 mg (2.2 mmol) of(3,4-bis-benzoyloxymethyl)benzyl bromide (obtained above) in 50 ml ofDMF is added. The mixture is stirred for 14 h, extracted between waterand ethyl acetate and separated after settling out. The organic phasesare dried over magnesium sulphate and evaporated. The residue obtainedis purified by chromatography on a silica column (heptane 80-ethylacetate 20) (m=1.1 g; Y=90%).

h)(E)-8-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol.

In a manner similar to Example 84(c), by reacting 1.1 g (1.8 mmol) ofethyl(E)-6-{3-[3,4-bis-(1-phenylmethanoyloxymethyl)]phenyl}hept-5-enoate with4.8 ml (14.5 mmol) of a 3M solution of ethylmagnesium bromide, acolourless oil is obtained (m=470 mg; Y=64%).

¹H NMR (CDCl₃): 0.86 (t, 6H, J=7.5 Hz), 1.38-1.57 (m, 8H), 2.00 (s, 3H),2.16-2.22 (m, 2H), 2.8 (bs, 2H), 4.76 (s, 2H), 4.77 (s, 2H), 5.08 (s,2H), 5.76 (t, 1H, J=7.2 Hz), 6.81-6.85 (m, 1H), 6.97-7.00 (m, 2H), 7.22(t, 1H, J=8.2 Hz), 7.39 (s, 2H), 7.45 (s, 1H).

EXAMPLE 908-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-nonan-3-ol

a) Ethyl 6-(3-Hydroxyphenyl)heptanoate.

In a manner similar to Example 64(b), starting with ethyl6-(3-hydroxyphenyl)hept-5-enoate, ethyl 6-(3-hydroxyphenyl)heptanoate isobtained in the form of an oil.

b) Ethyl 6-{3-[3,4-bis(1-Phenylmethanoyloxymethyl)]-phenyl}heptanoate.

In a manner similar to Example 89(a), by reacting ethyl6-(3-hydroxyphenyl)heptanoate with (3,4-bis-benzoyloxymethyl)benzylbromide, ethyl6-{3-(3,4-bis(1-phenylmethanoyloxymethyl)]phenyl}heptanoate is obtainedin the form of an oil

b) 8-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethylnonan-3-ol.

The product is obtained in a manner similar to Example 84(c) by additionof 4.5 ml of a 3.0M solution of ethylmagnesium bromide to 1 g (1.6 mmol)of ethyl 6-{3-[3,4-bis(1-phenylmethanoyloxymethyl)]-phenyl}heptanoate. Acolourless oil is obtained (m=490 mg; Y=66%).

¹H NMR (CDCl₃): 0.82 (t, 6H, J=7.5 Hz), 1.14-1.33 (m, 9H), 1.42 (q, 4H,J=7.5 Hz), 1.46-1.62 (m, 2H), 2.64 (m, 1H), 3.08 (bs, 2H), 4.73 (s, 2H),4.74 (s, 2H), 5.30 (s, 2H), 6.77-6.80 (m, 3H), 7.20 (t, 1H, J=8.2 Hz),7.37 (s, 2H), 7.42 (s, 1H).

EXAMPLE 91(4E,6E)-7-[5-(3,4-bis-Hydroxymethyl-benzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol

a) 5-Methoxymethoxy-2-methoxybenzaldehyde.

3 g (7.6 mmol) of NaH (60% in oil) are added to 9.6 g (63 mmol) of5-hydroxy-2-methoxybenzaldehyde in 150 ml of DMF and the mixture isstirred until the gaseous emission ceases. 5.3 ml (70 mmol) ofmethoxymethyl chloride are then added and the mixture is stirred at roomtemperature for two hours. After the usual treatment and chromatographyon silica, 12.3 g of the expected product are obtained (100%).

b) 3-(5-Methoxymethoxy-2-methoxyphenyl)-3-propanol.

12.3 g (63 mmol) of the above product in THF are reacted with 31 ml of a3M solution of ethylmagnesium bromide (93 mmol). After stirring for onehour and the usual treatment, the residue is purified by chromatographyon silica (ethyl acetate 20-heptane 80). 13.2 g (92%) of3-(5-methoxymethoxy-2-methoxyphenyl)-3-propanol are obtained.

c) 3-(5-Methoxymethoxy-2-methoxyphenyl)-3-propanone.

4.04 ml (43.3 mmol) of oxalyl chloride are dissolved in 150 ml ofdichloromethane and then the mixture is cooled to −78° C. A solution of6.58 ml (92.7 mmol) of DMSO in 20 ml of dichloromethane is then slowlyadded. When the the gaseous emission is over (after about 15 minutes), asolution of 5.3 g (23.1 mmol) of3-(5-methoxymethoxy-2-methoxyphenyl)-3-propanol and 3.3 ml oftriethylamine (23 mmol) in 50 ml of dichloromethane is added dropwise.After 20 minutes, 22.5 ml (162 mmol) of triethylamine are added and thenthe reaction medium is brought to room temperature and stirred for onehour. The medium is then treated with a saturated ammonium chloridesolution and then extracted with ethyl ether. The organic phase iswashed with water, dried and concentrated under reduced pressure. Theresidue is purified by chromatography on silica (ethyl acetate20-heptane 80); 5.2 g (100%) of expected ketone are recovered.

d) Ethyl 5-(5-Hydroxy-2-methoxyphenyl)hepta-2,4-dienoate.

In a manner similar to Example 63(c), by reacting 3.9 g (17 mmol) of3-(5-methoxymethoxy-2-methoxyphenyl)-3-propanone with 8.7 g (34.8 mmol)of ethyl 4-diethylphosphonocrotonate, ethyl5-(5-methoxymethoxy-2-methoxyphenyl)hepta-2,4-dienoate is obtained whichis converted to ethyl 5-(5-hydroxy-2-methoxyphenyl)hepta-2,4-dienoatewith concentrated sulphuric acid in ethanol 800 mg (17%).

e) (4E,6E)-7-(5-Hydroxy-2-methoxyphenyl)-3-ethylnona-4,6-dien-3-ol.

In a manner-similar to Example 82(a), starting with 520 mg (1.9 mmol) ofethyl 5-(5-hydroxy-2-methoxyphenyl)hepta-2,4-dienoate, 350 mg (64%) of(4E,6E)-7-(5-hydroxy-2-methoxyphenyl)-3-ethylnona-4,6-dien-3-ol areobtained in the form of an oil.

f)(4E,6E)-7-[5-(3,4-bis-Benzoyloxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol.

In a manner similar to Example 89(g), by reacting 350 mg (1.2 mmol) ofthe above product with 630 mg (1.44 mmol) of(3,4-bis-benzoyloxymethyl)benzyl bromide, 581 mg (75%) of expectedproduct are obtained.

g)(4E,6E)-7-[5-(3,4-bis-Hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol.

581 mg of7-[5-(3,4-bis-benzoyloxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol(0.89 mmol) are dissolved in 20 ml of a 2% potassium carbonate solutionin methanol and then the reaction medium is stirred for 5 hours. Aftertreating with a saturated ammonium chloride solution and extracting withethyl acetate, the organic phases are combined, dried and concentratedunder reduced pressure. The residue is purified by chromatography on asilica column. A yellow oil is obtained (m=284 mg; Y=72%).

¹H NMR (CDCl₃): 0.80 (t, 6H, J=7.6 Hz), 0.97 (t, 3H, J=7.4 Hz), 1.47 (q,4H, J=7.6 Hz), 2.41 (q, 2H, J=7.4 Hz), 3.25 (bs, 1H), 3.35 (bs, 1H),3.73 (s, 3H), 4.71 (s, 4H), 5.05 (s, 2H), 5.60 (d, 1H, J=15.3 Hz),. 5.94(dd, 1H, J1=15.3 Hz, J2=10.7 Hz), 6.14 (d, 1H, J=10.7 Hz), 6.67-6.88 (m,3H), 7.34-7.56 (m, 3H).

EXAMPLE 92(4E,6E)-7-[5-(3,4-bis-Hydroxymethyl-benzyloxy)-2-methylphenyl]-3-ethylnona-4,6-dien-3-ol

In a manner similar to Example 91, starting with5-hydroxy-2-methylbenzaldehyde,(4E,6E)-7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methylphenyl]-3-ethylnona-4,6-dien-3-olis obtained in the form of a clear oil.

¹H NMR (CDCl₃): 0.83-0.97 (m, 9H), 1.60 (q, 4H, J=7.6 Hz), 2.20 (s, 3H),2.49 (q, 2H, J=7.4 Hz), 2.83 (bs, 2H), 3.10 (bs, 1H), 4.75 (s, 4H), 5.03(s, 2H), 5.65 (d, 1H, J=15.3 Hz), 5.87 (d, 1H, J=11 Hz), 6.58 (dd, 1H,J1=15.3 Hz, J2=11 Hz), 6.74-6.81 (m, 2H), 7.06-7.09 (m, 1H), 7.36-7.43(m, 3H).

EXAMPLE 93(4E,6E)-7-[3-(3,4-bis-Hydroxymethyl-benzyloxy)-5-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol

In a manner similar to Examples 91(c-g), starting with(3-methoxy-5-methoxymethoxyphenyl)ethanone,(4E,6E)-7-[3-(3,4-bis-hydroxymethyl-benzyloxy)-5-methoxyphenyl]-3-ethylnona-4,6-dien-3-olis obtained in the form of a clear oil.

¹H NMR (CDCl₃): 0.87 (t, 6H, J=7.6 Hz), 1.60 (q, 4H, J=7.6 Hz), 2.16 (m,3H), 2.88 (bs, 2H), 3.80 (s, 3H), 4.76 (s, 2H), 4.77 (s, 2H), 5.05 (s,2H), 5.78 (d, 1H, J=15 Hz), 6.44-6.68 (m, 5H), 7.33-7.45 (m, 3H).

EXAMPLE 94(4E,6E)-7-[3-(3,4-bis-Hydroxymethyl-benzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol

In a manner similar to Example 91, starting with3-hydroxy-2-methoxybenzaldehyde,(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-olis obtained in the form of a clear oil.

¹H NMR (CDCl₃): 0.90-1.01 (m, 9H), 1.61 (q, 4H, J=7.6 Hz), 2.66 (q, 2H,J=7.6 Hz), 2.75 (bs, 2H), 3.79 (s, 3H), 4.78 (s, 4H), 5.12 (s, 2H), 5.68(d, 1H, J=15.3 Hz), 6.09 (d, 1H, J=11 Hz), 6.62 (dd, 1H, J1=15.3 Hz,J2=11 Hz), 6.77-6.96 (m, 3H), 7.40-7.46 (m, 3H).

EXAMPLE 95(4E,6E)-7-[3-(3,4-bis-Hydroxymethyl-benzyloxy)-4-methylphenyl]-3-ethylnona-4,6-dien-3-ol

In a manner similar to Example 91(c-g), starting with(3-methoxymethoxy-4-methylphenyl)ethanone,(4E,6E)-7-[3-(3,4-bis-hydroxymethyl-benzyloxy)-4-methylphenyl]-3-ethylnona-4,6-diene-3-olis obtained in the form of a clear oil.

¹H NMR (CDCl₃): 0.90 (t, 6H, J=7.5 Hz), 1.49 (bs, 1H), 1.60 (q, 4H,J=7.5 Hz), 2.04 (s, 3H), 2.26 (s, 3H), 3.08 (bs, 2H), 4.73 (s, 2H), 4.74(s, 2H), 5.09 (s, 2H), 5.76 (d, 1H, J=15 Hz), 6.41 (d, 1H, 10.9 Hz),6.62 (dd, 1H, J1=15 Hz, J2=10.9 Hz), 6.96-6.99 (m, 2H), 7.11 (d, 1H,J=8.0 Hz), 7.35-7.45 (m, 3H).

EXAMPLE 96 1-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]ethanoneO-(2-Hydroxy-2-methylpropyl)oxime

a) 1-(3-Methoxymethoxyphenyl)ethanone Oxime.

360 mg (2 mmol) of 1-(3-methoxymethoxyphenyl)ethanone are dissolved in30 ml of anhydrous ethanol. 417 mg (6 mmol) of hydroxylaminehydrochloride are added, followed by 6 ml of a 1N sodium hydroxidesolution. The mixture is heated under reflux for 2 hours and then thereaction medium is concentrated under reduced pressure. The residue istaken up in a mixture of diethyl ether and a solution of ammoniumchloride. After extracting with ether, the organic phases are combined,dried and concentrated under reduced pressure. The residue is purifiedby chromatography on a silica column. A yellow oil is obtained (m=342mg; Y=88%).

b) 1-(3-Methoxymethoxyphenyl)ethanone O-(2-Hydroxy-2-methylpropyl)oxime.

330 mg of 1-(3-methoxymethoxyphenyl)ethanone oxime (1.7 mmol) aredissolved in 10 ml of anhydrous THF. 180 mg (1.87 mmol) of sodiumtert-butoxide are then added and the mixture is stirred for 1 hour. 690l (7.6 mmol) of isobutylene oxide are then added and the mixture isheated under reflux for 15 hours. After treating with water, thereaction medium is extracted with ethyl ether and then the organicphases are combined, dried and concentrated under reduced pressure. Theresidue is purified by chromatography on a silica column. A yellow oilis obtained (m=215 mg; Y=48%).

c) 1-(3-Hydroxyphenyl)ethanone O-(2-Hydroxy-2-methylpropyl)oxime.

210 mg (0.78 mmol) of 1-(3-methoxymethoxyphenyl)ethanoneO-(2-hydroxy-2-methylpropyl)oxime are dissolved in 10 ml of methanol.200 l of sulphuric acid are added and the reaction medium is stirred for18 hours at room temperature. After treating with water and extractingwith ethyl ether, the organic phases are combined, dried and thenconcentrated under reduced pressure. The residue is purified bychromatography on a silica column. A pale yellow oil is obtained (m=175mg; Y=100%).

d) 1-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-ethanoneO-(2-Hydroxy-2-methylpropyl)oxime.

In a manner similar to Examples 84b and 91b, starting with 170 mg (0.76mmol) of 1-(3-hydroxyphenyl)ethanone O-(2-hydroxy-2-methylpropyl)oxime,197 mg (74%) of 1-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]ethanoneO-(2-hydroxy-2-methylpropyl)oxime are obtained in the form of acolourless oil.

¹H NMR (CDCl₃): 1.22 (s, 6H), 2.23 (s, 3H), 3.44 (bt, 1H), 3.58 (s, 1H),4.71 (t, 4H, J=5.6 Hz), 5.15 (s, 2H), 6.99-7.15 (m, 3H), 7.25-7.39 (m,4H).

EXAMPLE 971-{1-[3-(3,4-bis-Hydroxymethylbenzyloxy)-phenyl]-propoxy}-3-ethylpentan-3-ol

a) 1-(3-Methoxymethoxyphenyl)propan-1-ol.

11.6 g (69.8 mmol) of 3-methoxymethoxybenzaldehyde are dissolved in 40ml of anhydrous THF. The mixture is cooled to 0° C. and is then added toan ethylmagnesium bromide solution (139 mmol) in 100 ml of ethyl ether.The reaction medium is brought to room temperature and then stirred for4 hours. After treating with an ammonium chloride solution andextracting with ethyl ether, the organic phases are combined, dried andconcentrated under reduced pressure. The residue is filtered on a silicalayer and then concentrated again in order to obtain a yellow oil(m=12.9 g; Y=94%).

b) Ethyl 3-[1-(3-Methoxymethoxyphenyl)propoxy]-propionate.

2.9 g (9.8 mmol) of 1-(3-methoxymethoxyphenyl)propan-1-ol and 4.24 ml(39 mmol) of ethyl acrylate are dissolved in 10 ml of anhydrous THF.This solution is then added to a 60% suspension of sodium hydride (390mg, 9.8 mmol) in 5 ml of THF maintained at 0° C. The medium is broughtto room temperature and then stirred for 48 hours. The medium is thentreated with an ammonium chloride solution and extracted with ethylacetate. The organic phases are combined, dried and then concentratedunder reduced pressure. The residue is purified by chromatography on asilica column (heptane eluent). A yellow oil is obtained (m=700 mg;Y=24%).

c) Ethyl 3-[1-(3-Hydroxyphenyl)propoxy]propionate.

1.09 g (36.8 mmol) of ethyl3-[1-(3-methoxymethoxyphenyl)propoxyl]propionate are dissolved in 30 mlof ethanol. 500 l of sulphuric acid are then added and the medium isstirred at room temperature for 15 minutes. After hydrolysis andextraction with ethyl acetate, the organic phases are combined, driedand concentrated under reduced pressure. The residue is purified bychromatography on a silica column. A yellow oil is obtained (m=520 mg;Y=56%).

d)1-{-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-propoxy}-3-ethylpentan-3-ol.

In a manner similar to Examples 84(b, c), 520 mg of ethyl3-[1-(3-hydroxyphenyl)propoxy]-propionate (2.06 mmol) are converted to1-{1-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]propoxy}-3-ethylpentan-3-ol,in the form of a pale yellow oil (m=260 mg; Y=30%).

¹H NMR (CDCl₃): 0.64-0.74 (m, 9H), 1.24-1.42 (m, 4H), 1.47-1.63 (m, 4H),3.16 (bs, 3H), 3.32-3.38 (m, 2H), 3.90-4.00 (m, 1H), 4.59 (s, 2H), 4.60(s, 2H), 4.94 (s, 2H), 6.69-6.78 (m, 3H), 7.08-7.29 (m, 4H).

EXAMPLE 98(E)-7-[3-(3,4-bis-Hydroxymethylphenoxy-methyl)phenyl]-3-ethylnon-6-en-3-ol

a) Methyl (E)-5-(3-Bromophenyl)hex-4-enoate.

19.3 g (44.9 mmol) of (3-carboxypropyl)triphenylphosphonium bromide aredried under vacuum for 1 h and by heating 130° C. and then brought toroom temperature and dissolved in 200 ml of anhydrous THF. 10.1 g (89.8mmol) of potassium tert-butoxide in 100 ml of THF are then slowly addedand then the orange-red mixture is stirred for 15 minutes. A solution of6.4 g (29.9 mmol) of 1-(3-bromophenyl)propanone in 100 ml of THF is thenadded dropwise and the reaction medium is stirred for 15 hours. Aftertreating with a saturated ammonium chloride solution and extracting withethyl acetate and then drying and evaporating the solvents of theorganic phase, the residue is purified by chromatography on a silicacolumn. A yellow oil is obtained (m=6.2 g; Y=74%). This product is thendissolved in 100 ml of methanol and then 2 ml of sulphuric acid areadded. The reaction medium is heated under reflux and stirred for 2hours. After treating with water, the medium is extracted with ethylacetate and then the organic phases are combined, dried and concentratedunder reduced pressure. The residue is purified by chromatography on asilica column (eluent heptane 95-ethyl acetate 5) in order to obtain thepure trans isomer in the form of a yellow oil (m=6.5 g; Y=74% total).

b) (E)-7-(3-Bromophenyl)-3-ethylnon-6-en-3-ol.

6.49 g of ethyl (E)-5-(3-bromophenyl)hept-4-enoate (21.8 mmol) aredissolved in 100 ml of ethyl ether. 29 ml of a 3.0M solution ofethylmagnesium bromide (87 mmol) are then added dropwise and thereaction medium is stirred at room temperature for 1 hour. Aftertreating with a saturated ammonium chloride solution, extracting withethyl ether and then drying and evaporating the solvents of the organicphase, the residue is purified by chromatography on a silica column; acolourless oil is obtained (m=6.79 g; Y=97%).

c) ((E)-5-(3-Bromophenyl)-1,1-diethylhept-4-enyloxy]-triethylsilane.

6.79 g (20.9 mmol) of (E)-7-(3-bromophenyl)-3-ethylnon-6-en-3-ol aredissolved in 100 ml of dichloromethane. 75 mg (0.6 mmol) of4-dimethyllaminopyridine and 14.5 ml of triethylamine (104 mmol) areadded and the reaction medium is cooled to 0° C. 11.8 ml (52 mmol) oftriethylsilyltrifluoromethanesulphonate are added dropwise. After theaddition, the reaction medium is brought to room temperature and thentreated with water and extracted with dichloromethane. After drying andconcentrating the organic phases under reduced pressure, the residue ispurified by chromatography on a silica column; a yellow oil is obtained(m=9.1 g; Y=99%).

d) [3-((E)-1,5-Diethyl-5-triethylsilanyloxyhept-1-enyl)phenyl]methanol.

9.1 g (20.5 mmol) of[(E)-5-(3-bromophenyl)-1,1-diethylhept-4-enyloxy]triethylsilane aredissolved in 130 ml of anhydrous THF and then the mixture is cooled to−78° C. 9.18 ml (23 mmol) of a 2.5M solution of butyllithium are thenadded and then the reaction medium is stirred for 15 minutes. 1.78 ml ofanhydrous DMF (23 mmol) are then added and then the reaction medium isbrought to room temperature and stirred for 1 h. After treating with asaturated ammonium chloride solution and then extracting with ethylacetate, the organic phases are combined, dried and concentrated underreduced pressure. The residue containing the desired(E)-5-ethyl-1-ethyl-5-triethylsilanyloxyhept-1-enyl)benzene-2-carbaldehydeis then dissolved in 100 ml of anhydrous methanol and then 760 mg (20mmol) of sodium borohydride are added in two portions. After stirringfor 10 minutes, the medium is treated with a solution of ammoniumchloride and extracted with ethyl ether. The organic phases arecombined, dried and concentrated under reduced pressure. Afterpurification by chromatography on-a silica column, a yellow oil isobtained (m=2 g; Y=25%).

e) Dimethyl4-[3-((E)-1,5-Diethyltriethylsilanyloxyhept-1-enyl)phenylmethoxy]phthalate.

300 mg (0.77 mmol) of[3-((E)-1,5-diethyl-5-triethylsilanyloxyhept-1-enyl)phenyl]-methanol aredissolved in 20 ml of dichloromethane and cooled to 0° C. 0.16 ml (1.1mmol) of triethylamine is added, followed by 65 l of methylsulphonatechloride (0.85 mmol). After stirring for 20 minutes, the reaction mediumis treated with an ammonium chloride solution and extracted withdichloromethane. The organic phases are combined, dried and concentratedunder reduced pressure. The residue obtained is then dissolved in 20 mlof 2-butanone, and 244 mg of dimethyl 4-hydroxyphthalate (1.16 mmol),160 mg of potassium carbonate (1.16 mmol) and 10 mg of sodium iodide areadded. The mixture is heated under reflux for 6 hours and then cooledand filtered. The filtrate is concentrated under reduced pressure andthen purified by chromatography on a silica column. A yellow oil isobtained (m=355 mg; Y=79%).

f){4-[3-((E)-1,5-Diethyl-5-triethylsilanoxyhept-1-enyl)phenoxymethyl]-2-hydroxymethylphenyl}methanol.

1.28 g (2.2 mmol) of dimethyl4-[3-((E)-1,5-diethyl-5-hydroxyhept-1-enyl)phenylmethoxy]-phthalate aredissolved in 40 ml of anhydrous ethyl ether. 200 mg (5.3 mmol) oflithium aluminium hydride are added and the reaction medium is stirredat room temperature for 30 minutes. 200 l of water, 200 l of 15% NaOHand 600 1 of water are then slowly added and the medium is filtered. Thefiltrate is concentrated under reduced pressure and then the residue ispurified by chromatography on a silica column (ethyl acetate 70-heptane30). A colourless oil is obtained (m=1.03 mg; Y=89%).

g)(E)-7-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-3-ethylnon-6-en-3-ol.

1.03 g (1.96 mmol) of{4-[3-((E)-1,5-diethyl-5-triethylsilanoxyhept-1-enyl)phenoxymethyl]-2-hydroxymethylphenyl}methanolare dissolved in 30 ml of THF. 3.9 ml (3.9 mmol) of a tetrabutylammoniumfluoride solution (1M in THF) are added and the reaction medium isheated at 60° C. for 3 hours. After treating with an ammonium chloridesolution and extracting with ethyl acetate, the organic phases arecombined, dried and concentrated under reduced pressure. The residue ispurified by chromatography on a silica column. A colourless oil isobtained (m=198 mg; Y=24%).

¹H NMR (CDCl₃): 0.69 (t, 6H, J=7.6 Hz), 0.91 (t, 3H, 7.5 Hz), 1.40-1.50(m, 6H), 2.14 (q, 2H, J=7.6 Hz), 2.45 (q, 2H, J=7.5 Hz), 2.8 (bs, 1H),3.15 (bs, 1H), 4.59 (s, 2H), 4.61 (s, 2H), 4.99 (s, 2H), 5.57 (t, 1H,J=7.3 Hz), 6.79-6.95 (m, 2H), 7.10-7.31 (m, 5H).

EXAMPLE 99(E)-7-[3-(3,4-bis-Hydroxymethylbenzyl-sulphanyl)phenyl]-3-ethyloct-6-en-3-ol

a) (E)-5-(3-Dimethylcarbamoylsulphanylphenyl)hex-4-enoic Acid.

4 g (17.9 mmol) of dimethylthiocarbamic acid S-(3-acetylphenyl) esterare subjected to the same conditions described in Example 98(a) andafter chromatography on a silica gel, the acid is obtained in the formof a thick oil (m=3 g; Y=56%).

b) Methyl(E)-5-{3-[3-(4-Methoxycarbonyl-1-methylbut-1-enyl)phenyldisulphanyl]phenyl}hex-4-enoate.

1.5 g of (E)-5-(3-dimethylcarbamoylsulphanylphenyl)hex-4-enoic acid aredissolved in 30 ml of a 1:1 mixture of water and ethanol. 400 mg of NaOHare added and the reaction medium is heated under reflux for 18 hours.The medium is then treated with a 1N solution of hydrogen chloride andthen extracted with ethyl acetate. The organic phases are then combined,dried and concentrated under reduced pressure. The residue is thendissolved in 30 ml of methanol and 1 ml of sulphuric acid is added. Thereaction medium is then stirred under reflux for 15 hours and thencooled and treated with water. After extraction with ethyl acetate,drying and concentrating the organic phases, the residue is purified bychromatography on a silica gel. A yellow oil is obtained (m=360 mg;Y=30%).

c) Methyl(E)-5-[3-(3,4-bis-Hydroxymethylbenzylsulphanyl)phenyl]hex-4-enoate.

200 mg (0.4 mmol) of methyl(E)-5-{3-[3-(4-methoxycarbonyl-1-methylbut-1-enyl)phenyldisulphanyl]phenyl}hex-4-enoateand 370 mg (0.84 mmol) of dimethyl 4-bromomethylphthalate are dissolvedin 10 ml of dichloromethane. 140 mg (2.1 mmol) of zinc powder are thenadded and 100 l of acetic acid are added. The reaction medium is thenstirred for 24 hours at room temperature and then treated with water andextracted with dichloromethane. The organic phases are combined, driedand concentrated under reduced pressure. After purification bychromatography on a silica gel, a yellow oil is obtained (m=100 mg;Y=40%).

d)(E)-7-[3-(3,4-bis-Hydroxymethylbenzylsulphanyl)phenyl]-3-ethyloct-6-en-3-ol.

In a manner similar to Example 84(c), 140 mg (0.24 mmol) of methyl(E)-5-[3-(3,4-bis-hydroxymethylbenzylsulphanyl)phenyl]hex-4-enoate aretreated with 1 ml (2 mmol) of an ethylmagnesium chloride solution. Afterpurification on a silica column, a colourless oil is obtained (m=70 mg;Y=70%).

¹H NMR (DMSO): 0.84 (t, 6H, J=7.3 Hz), 1.37-1.48 (m, 6H), 1.98 (s,. 3H),2.14-2.19 (m, 2H), 3.94 (s, 1H), 4.28 (s, 2H), 4.53 (t, 4H, J=5.2 Hz),5.08 (t, 1H, J=5.2 Hz), 5.14 (t, 1H, J=5.2 Hz), 5.83 (t, 1H), 7.20-7.48(m, 7H).

EXAMPLE 100(E)-7-{3-[(3,4-bis-Hydroxymethylbenzyl)methylamino]-phenyl)-3-ethyloct-6-en-3-ol

a) Dimethyl4-({Methoxycarbonyl-[3-(2-methyl-[1,3]dioxolan-2-yl)phenyl]amino}methyl)phthalate.

4 g (22.3 mmol) of 3-(2-methyl-[1,3]dioxolan-2-yl)phenylamine aredissolved in 30 ml of anhydrous toluene. 1.85 ml (24 mmol) of methylchloroformate and 1.57 g (24 mmol) of zinc powder are suspended in 30 mlof toluene and stirred at room temperature.

The solution prepared above is then added dropwise by means of a smalltube and then the reaction medium is stirred for 1 hour. The reactionmedium is then filtered and the solid residue rinsed with ethyl acetate.The organic phases are washed with a saturated sodium bicarbonatesolution and then dried and concentrated under reduced pressure. Theresidue is dissolved in 50 ml of anhydrous DMF and the mixture is cooledto 0° C. 1.04 g (24 mmol) of sodium hydride are then added and thestirring is continued for 30 minutes. A solution of dimethyl4-bromomethylphthalate (26 mmol) in 10 ml of DMF is then added, thereaction medium is stirred at room temperature for 2 hours and thentreated with a saturated ammonium chloride solution and extracted withether. The organic phases are combined, dried and concentrated underreduced pressure. The residue is purified by chromatography on a silicacolumn. A yellow oil is obtained (m=6.5 g; Y=67%).

b) 1-{3-[(3,4-bis-Hydroxymethylbenzyl)methylamino]-phenyl}ethanone.

6.5 g of dimethyl4-((methoxycarbonyl-[3-(2-methyl[1,3]dioxolan-2-yl)phenyl]amino}methyl)phthalate(14.6 mmol) are dissolved in 200 ml of anhydrous THF and the mixture iscooled to 0° C. 2.8 g (74 mmol) of lithium aluminium hydride are addedin three portions and the mixture is heated under reflux for 4 hours.After cooling, the reaction medium is successively treated with 2.8 mlof water. 2.8 ml of 15% NaOH and 8.4 ml of water. The medium is dilutedwith 200 ml of ethyl ether, stirred for 1 hour and then filtered. Thefiltrate is evaporated under reduced pressure and the residue isdissolved in 100 ml of methanol. 5 g of silica gel are added as well as100 1 of sulphuric acid and the reaction medium is stirred for 24 hoursand then filtered and rinsed with a 0.5M solution of NaOH. The organicphase is dried and concentrated under reduced pressure. A colourless oilis obtained (m=3.98 mg; Y=91%).

c)1-(3-{[3,4-bis(tert-Butyldimethylsilanyloxymethyl)benzyl]methylamino}phenyl)ethanone.

3.89 g (13 mmol) of1-{3-[(3,4-bis-hydroxymethylbenzyl)methylamino]phenyl}ethanone aredissolved in 20 ml of anhydrous DMF. tert-Butyldimethylsilane chloride(4.7 g; 31 mmol) is added and then 2.48 g (36.4 mmol) of imidazole areadded. The medium is stirred at room temperature for 4 hours and thendiluted with 100 ml of ethyl ether and filtered. The filtrate is washedwith an ammonium chloride solution and then with water and the organicphase is dried and then concentrated under reduced pressure. The residueis purified by chromatography on a silica column in order to obtain avery thick colourless oil (m=5.83 g; Y=85%).

d)(E)-5-{3-[(3,4-bis(tert-Butyldimethylsilanyloxymethyl)benzyl)methylamino]phenyl}hex-4-enoicAcid.

2.85 g (6.6 mmol) of (3-carboxypropyl)triphenylphosphonium bromide aredried under vacuum at 130° C. for 1 hour and then dissolved in 50 ml ofanhydrous THF. 1.48 g (13.3 mmol) of potassium tert-butoxide are addedand the orange-red mixture is stirred for 15 minutes.

1 g (1.9 mmol) of1-(3-{[3,4-bis(tert-butyldimethylsilanyloxymethyl)benzyl]methylamino}phenyl)ethanoneis dissolved in 10 ml of THF and added dropwise to the above suspension.The medium is then stirred for 5 hours and then treated with a 1Nsolution of hydrochloric acid and extracted with ethyl ether. Theorganic phases are dried and concentrated under reduced pressure. Theresidue is purified by chromatography on a silica column. A colourlessoil is obtained (m=570 mg; Y=49%).

e)(E)-7-{3-[(3,4-bis-Hydroxymethylbenzyl)methylamino]phenyl}-3-ethyloct-6-en-3-ol.

550 mg (0.9 mmol) of(E)-5-{3-[(3,4-bis(tert-butyldimethylsilanyloxymethyl)benzyl)methylamino]-phenyl}hex-4-enoicacid are dissolved in 20 ml of anhydrous methanol and then 0.5 ml ofsulphuric acid are added and the mixture is heated under reflux for 24hours. The reaction medium is then treated with water and extracted withdichloromethane. The organic phases are dried and then concentratedunder reduced pressure. The residue is dissolved in 10 ml of THF andtreated with 1.5 ml (4.5 mmol) of an ethylmagnesium bromide solution.The reaction medium is stirred at room temperature for 1 hour and thentreated with an ammonium chloride solution and extracted with ethylacetate. The organic phases are dried and concentrated under reducedpressure and the residue is purified by chromatography on a silicacolumn. A colourless oil is obtained (m=277 mg; Y=71%).

¹H NMR (DMSO): 0.66 (t, 6H, J=7.3 Hz), 1.19-1.28 (m, 6H), 1.76 (s, 3H),1.90-2.00 (m, 2H), 3.21 (s, 3H), 4.09 (d, 2H, J=5.7 Hz), 4.37 (t, 4H,J=5.2 Hz), 4.88 (t, 1H, J=5.2 Hz), 4.94 (t, 1H, J=5.2 Hz), 5.60 (t, 1H),6.05 (t, 1H), 6.30 (d, 1H), 6.48 (d, 1H), 6.55 (s, 1H), 6.81 (t, 1H),7.08 (d, 1H), 7.16 (d, 1H), 7.27 (s, 1H).

EXAMPLE 101(E)-6-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-6-methylhept-4-en-3-ol

a) Methyl 2-[3-(tert-Butyldimethylsilanyloxy)phenyl]-2-methylpropionate.

10 g of methyl [3-(tert-butyldimethylsilanyloxy)phenyl]acetate (35.6mmol) are dissolved in 200 ml of anhydrous THF. 35.6 ml of a 2.0Msolution of lithium diisopropylamide are then added and then the mediumis stirred for 30 minutes. 8.9 ml (142 mmol) of methyl iodide are addedand the reaction medium is stirred at room temperature for 40 hours.After treating with an ammonium chloride solution and then extractingwith ethyl ether, the organic phases are combined, washed with asaturated sodium chloride solution, dried and concentrated under reducedpressure. A colourless oil is obtained (m=10.8 g; Y=98%).

b) 2-[3-(tert-Butyldimethylsilanyloxy)phenyl]-2-methylpropan-1-ol.

10.8 g of methyl2-[3-(tert-butyldimethylsilanyloxy)phenyl]-2-methylpropionate (35 mmol)are dissolved in 150 ml of anhydrous THF. 4 portions of 500 mg each oflithium aluminium anhydride (52.5 mmol) are added and the medium isstirred at room temperature for 3 hours. After treating successivelywith 2 ml of water, 2 ml of 15% NaOH and then 6 ml of water, thereaction medium is diluted by the addition of 200 ml of ethyl ether andthen filtered, and the filtrate concentrated under reduced pressure. Acolourless oil is obtained (m=9.7 g; Y=99%).

c) Ethyl(E)-4-[3-(tert-Butyldimethylsilanyloxy)phenyl]-4-methylpent-2-enoate.

4.04 ml (43.3 mmol) of oxalyl chloride are dissolved in 150 ml ofdichloromethane and then the mixture is cooled to −78° C. A solution of6.58 ml (92.7 mmol) of DMSO in 20 ml of dichloromethane is then slowlyadded. When the emission of gas is over (after about 15 minutes), asolution of 6.5 g (23.1 mmol) of2-[3-(tert-butyldimethylsilanyloxy)phenyl]-2-methylpropan-1-ol and 3.3ml of triethylamine (23 mmol) in 50 ml of dichloromethane is addeddropwise. After 20 minutes, 22.5 ml (162 mmol) of triethylamine areadded and then the reaction medium is brought to room temperature andstirred for 1 hour. The medium is then treated with a saturated ammoniumchloride solution and then extracted with ethyl ether. The organic phaseis washed with water, dried and concentrated under reduced pressure. Theresidue obtained is then dissolved in 100 ml of anhydrous THF.

In another round-bottomed flask, 9.2 ml (46.3 mmol) oftriethylphosphonoacetate are dissolved in 100 ml of anhydrous THF andthe the mixture is cooled to 0° C. 22 ml (44 mol) of a 2.0M solution oflithium diisopropylamide is then added and the medium is stirred at 0°C. for 30 minutes. The solution prepared above is then added with theaid of a small tube and the reaction medium is brought to roomtemperature and then stirred for 15 hours. After treating with asaturated ammonium chloride solution and then extracting with ethylether, the organic phases are combined, dried and concentrated underreduced pressure. The residue is purified by chromatography on a silicacolumn. A colourless oil is obtained (m=6.28 g; Y=78%).

d) Ethyl (E)-4-(3-Hydroxyphenyl)-4-methylpent-2-enoate.

400 mg (1.14 mmol) of ethyl(E)-4-[3-(tert-butyldimethylsilanyloxy)phenyl]-4-methylpent-2-enoate aredissolved in 20 ml of anhydrous THF and then 1.5 ml of atetrabutylammonium fluoride solution (1M in THF) (1.5 mmol) is added.The reaction medium is immediately concentrated under reduced pressureand purified by chromatography. A colourless oil is obtained (m=262 mg;Y=98%).

e)(E)-6-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-6-methylhept-4-en-3-ol.

In a manner similar to Examples 84(b, c), starting with 262 mg of ethyl(E)-4-(3-hydroxyphenyl)-4-methylpent-2-enoate (1.12 mmol),(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-6-methylhept-4-en-3-olis obtained in the form of a colourless oil (m=355 mg; Y=79%).

¹H NMR (DMSO): 0.71 (t, 6H, J=7.3 Hz), 1.25 (s, 6H), 1.36 (q, 4H, J=7.3Hz), 4.03 (s, 1H), 4.47 (t, 4H, J=4.7 Hz), 4.96 (s, 2H), 5.02 (t, 1H,J=4.7 Hz), 5.06 (t, 1H, J=4.7 Hz), 5.23 (d, 1H, J=15.9 Hz), 5.64 (d, 1H,J=15.9 Hz), 6.72-6.87 (m, 3H),. 7.13 (t, 1H, J=7.8 Hz) 7.22 (d, 1H, 7.7Hz), 7.31 d, 1H, J=7.7 Hz), 7.40 (s, 1H).

EXAMPLE 1027-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctan-3-ol

a) 4-[3-(tert-Butyldimethylsilanyloxy)phenyl]-4-methylpentan-1-ol.

6.15 g (17.6 mmol) of ethyl(E)-4-[3-(tert-butyldimethylsilanyloxy)phenyl]-4-methylpent-2-enoate(101 c) are dissolved in 150 ml of anhydrous methanol and the mixture iscooled to 0° C. 1.28 g (52.8 mmol) of magnesium chips are added and thereaction medium is stirred for 4 hours at 0° C. After treating with asaturated ammonium chloride solution and then extracting with ethylacetate, the organic phases are combined, dried and concentrated underreduced pressure. The residue is then dissolved in 100 ml of anhydrousTHF and 1 g (26.4 mmol) of lithium aluminium hydride is added. Afterstirring for 1 hour at room temperature, the medium is treatedsuccessively with 1 ml of water, 1 ml of 15% NaOH, 3 ml of water anddiluted by the addition of 150 ml of ethyl ether. After filtration, thefiltrate is concentrated under reduced pressure. A colourless oil isobtained (m=3.8 g; Y=70%).

b)tert-Butyl-[3-(4-[1,3]dithian-2-ylidene-1,1-dimethylbutyl)phenoxy]dimethylsilane.

1.94 ml (22.2 mmol) of oxalyl chloride are dissolved in 100 ml ofdichloromethane and then the mixture is cooled to −78° C. A solution of3.15 ml (44.4 mmol) of DMSO in 10 ml of dichloromethane is then slowlyadded. When the emission of gas is over (after about 15 minutes), asolution of 3.43 g (11.1 mmol) of4-[3-(tert-butyldimethylsilanyloxy)phenyl]-4-methylpentan-1-ol and 1.6ml of triethylamine (11.1 mmol) in 50 ml of dichloromethane is addeddropwise. After 20 minutes, 10.8 ml (77.7 mmol) of triethylamine areadded and then the reaction medium is brought to room temperature andstirred for 1 hour. The medium is then treated with a saturated ammoniumchloride solution and then extracted with ethyl ether. The organic phaseis washed with two fractions of ammonium chloride and then with water,dried and concentrated under reduced pressure. The residue obtained isthen dissolved in 100 ml of anhydrous THF.

In another round-bottomed flask, 2.31 ml (12.2 mmol) of2-trimethylsilyl-1,3-dithiane are dissolved in 50 ml of anhydrous THFand the mixture is cooled to −78° C. 4.88 ml. of a 2.5M solution ofbutyllithium (12.2 mmol) are added. The reaction medium is stirred for30 minutes at −78° C. and then the solution prepared above is addeddropwise. The medium is again stirred for 4 hours at −78° C. and thenbrought to room temperature and treated with an ammonium chloridesolution. After extracting with ethyl ether, the organic phases arecombined, dried and concentrated under reduced pressure. The residue ispurified by chromatography on a silica column. A yellow oil is obtained(m=3.54 g; Y=78%).

c) Methyl 5-(3-Hydroxyphenyl)-5-methylhexanoate.

3.4 g (8.4 mmol) oftert-butyl-[3-(4-[1,3]dithian-2-ylidene-1,1-dimethylbutyl)phenoxy]-dimethylsilaneare dissolved in 200 ml of acetonitrile and 50 ml of water. 2.1 g (21mmol) of calcium carbonate and then 5 g (18.5 mmol) of mercurydichloride are added. After stirring for 48 hours at room temperature,the reaction medium is treated with a saturated ammonium chloridesolution and then extracted with ethyl acetate. The organic phases arecombined and then washed with a 1N hydrochloric acid solution and withwater, and finally dried and concentrated under reduced pressure. Theresidue is dissolved in 150 ml of methanol, and 2 ml of sulphuric acidare added. The reaction medium is heated under reflux for 15 hours andthen treated with water and extracted with ethyl ether. The organicphases are combined, dried and concentrated under reduced pressure. Theresidue is purified by chromatography on a silica column. A colourlessoil is obtained (m=1.1 g; Y=56%).

d)7-[3-(3,4-bis-Hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctan-3-ol.

In a manner similar to Example 101(e), 1 g of methyl5-(3-hydroxyphenyl)-5-methylhexanoate (4.2 mmol) are converted to7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctan-3-ol,in the form of a white crystalline solid (m.p.=88-89° C; m=700 mg;Y=40%).

¹H NMR (DMSO): 0.50 (t, 6H, J=7.3 Hz), 0.78-0.84 (m, 2H), 0.96-1.07 (m,12H), 1.30-1.36 (m, 2H), 3.50 (s, 1H), 4.35 (t, 4H, J=4.9 Hz), 4.86 (s,2H), 4.90 (t, 1H, J=4.9 Hz), 4.94 (t, 1H, J=4.9 Hz), 6.60-6.73 (m, 3H),7.01 (t, 1H, J=7.8 Hz) 7.11 (d, 1H, 7.7 Hz), 7.20 (d, 1H, J=7.7 Hz),7.29 (s, 1H).

EXAMPLE 103(E)-3-Ethyl-7-[3-(4-hydroxymethyl-3-methylphenoxy-methyl)phenyl]non-6-en-3-ol

a) 4-iodo-3-Methylphenol

15 g (122 mol) of 4-hydroxy-2-methylaniline are dissolved in 180 ml of20% sulphuric acid and then the reaction medium is cooled to 0° C. Asolution of sodium nitrite (11.3 g, 163 mmol) in 60 ml of water is thenadded dropwise and then the medium is stirred for 20 minutes. Thissolution is then slowly added to a solution at 0° C. of CuI (32.5 g, 170mmol) and KI (31.9 g, 193 mmol) in 180 ml of 20% sulphuric acid. Thereaction medium is heated under reflux for 3 hours, poured into 1 l ofwater and extracted with ethyl ether. The organic phases are washed witha saturated sodium thiosulphate solution, of water, dried over magnesiumsulphate and concentrated under reduced pressure. After purification ona silica column (ethyl acetate 30-heptane 70), a brown oil is obtained(m 4.2 g; Y=15%).

b) Methyl 4-Hydroxy-2-methylbenzoate

4.2 g (18 mmol) of 4-iodo-3-methylphenol are dissolved in 90 ml ofanhydrous methanol and then placed in a steel reactor. 5 ml (35 mmol) oftriethylamine and 400 mg (1.8 mmol) of palladium diacetate are added,the reaction medium is subjected to a carbon monoxide pressure of 3 barand heated at 80° C. for 5 hours. The medium is then brought to ambientpressure and temperature and then dissolved in dichloromethane andfiltered on celite. After evaporation, the residue is purified bychromatography on a silica column. An orange-coloured powder is obtained(m=1.8 g, Y=61 g).

c)(E)-3-Ethyl-7-[3-(4-hydroxymethyl-3-methylphenoxymethyl)phenyl]non-6-en-3-ol

In a manner identical to Examples 98 e, f, g, by reacting methyl4-hydroxy-2-methylbenzoate with[3-((E)-5-ethyl-1-methyl-5-triethylsilanyloxyhept-1-enyl)phenyl]methanol(obtained in Example 98 d) and then treating successively with lithiumaluminium hydride and then with tetrabutylammonium fluoride, a thickwhite oil is obtained.

¹H NMR (DMSO): 0.64 (t, 6H, J=7.5 Hz), 0.77 (t, 3H, J=7.3 Hz), 1.18-1.29(m, 6H), 1.94-2.03 (m, 2H), 2.07 (s, 3H), 2.28-2.38 (m, 2H), 3.74 (s,1H), 4.24 (d, 2H, J=5.2 Hz), 4.73 (t, 1H, J=5.2 Hz), 4.90 (s, 2H), 5.52(t, 1H, J=7.3 Hz), 6.60-6.65 (m, 2H), 7.03-7.17 (m, 4H), 7.26 (s, 1H).

EXAMPLE 104(E)-3-Ethyl-7-[3-(3-hydroxymethyl-4-methylphenoxymethyl)phenyl]non-6-en-3-ol

a) Methyl 2-Methyl-5-nitrobenzoate

23.2 g (88 mmol) of 2-iodo-4-nitrotoluene are dissolved in 400 ml ofanhydrous methanol and then placed in a steel reactor. 25 ml (177 mmol)of triethylamine, 1.97 g (8.8 mmol) of palladium diacetate and 7.3 g ofdiphenyphosphinopropane are added and the reaction medium is subjectedto a carbon monoxide pressure of 4 bar and heated at 110° C. for 18hours. The medium is then brought to ambient pressure and temperature,dissolved in dichloromethane and filtered on celite. After evaporation,the residue is purified by chromatography on a silica column. Anorange-coloured powder is obtained (m=6.3 g, Y=37%).

b) Methyl 3-Amino-6-methylbenzoate

6.3 g (32 mmol) of methyl 2-methyl-5-nitrobenzoate are dissolved in 80ml of anhydrous methanol and then transferred into a steel reactor. Themixture is degassed with nitrogen and then 630 mg of Pd/C (5%) areadded. The reaction medium is then subjected to a hydrogen pressure of 4bar and to a temperature of 80° C. for 14 hours and then brought toambient pressure and temperature and filtered. The residue, afterevaporation, is purified by chromatography on a silica column. A brownoil is obtained (m=4.6 g, Y=86%).

c) Methyl 3-Hydroxy-6-methylbenzoate

4.6 g (28 mmol) of methyl 3-amino-6-methylbenzoate are dissolved in 50ml of THF and 50 ml of 1M sulphuric acid and then the reaction medium iscooled to 0° C. A solution of sodium nitrite (2.3 g, 33.6 mmol) in 10 mlof water is then added dropwise and then the medium is stirred for 20minutes. 15 ml of pure sulphuric acid are then added and the reactionmedium is heated under reflux for 2 hours, poured into 500 ml of waterand extracted with ethyl ether. The organic phases are dried,concentrated under reduced pressure and the residue obtained isdissolved in 100 ml of methanol. 3 ml of sulphuric acid are added andthe reaction medium is heated under reflux for 14 hours, cooled, treatedwith water and ethyl ether. After extraction with ethyl ether, theorganic phases are combined, dried over magnesium sulphate andconcentrated under reduced pressure. After purification on a silicacolumn (ethyl acetate 30-heptane 70), a brown oil is obtained (m=1.2 g;Y=25%).

c)((E)-3-Ethyl-7-[3-(3-hydroxymethyl-4-methylphenoxymethyl)phenyl]non-6-en-3-ol

In a manner identical to Examples 98 e, f, g, by reacting methyl3-hydroxy-6-methylbenzoate with[3-((E)-5-ethyl-1-methyl-5-triethylsilanyloxyhept-1-enyl)phenyl]methanol(obtained in Example 98 d), and then treating successively with lithiumaluminium hydride and then with tetrabutylammonium fluoride, acolourless oil is obtained.

¹H NMR (DMSO): 0.73 (t, 6H, J=7.5 Hz), 0.85 (5, 3H, J=7.3 Hz), 1.26-1.38(m, 6H), 2.02-2.12 (m, 5H), 2.38-2.46 (m, 2H), 3.82 (s, 1H), 4.36 (d,2H, J=5.4 Hz), 4.98-5.03 (m, 3H), 5.61 (t, 1H, J=7.2 Hz), 6.68-6.72 (m,1H), 6.93-6.96 (m, 2H), 7.22-7.25 (m, 3H), 7.35 (s, 1H).

EXAMPLE 105(E)-7-[3-(3,4-bis-Hydroxymethylphenoxymethyl)phenyl]-3-ethyloct-6-en-3-ol

In a manner similar to Example 98,(E)-7-[3-(3,4-bishydroxymethyl)phenoxymethyl)phenyl]-3-ethyloct-6-en-3-olis obtained in the form of a white powder m.p.=89-91° C.).

¹H NMR (DMSO): 0.67 (t, 6H, J=7.4 Hz), 1.21-1.33 (m, 6H), 1.86 (d, 3H,J=2.2 Hz), 1.94-2.06 (m, 2H), 3.78 (s, 1H), 4.30 (d, 2H, J=5.3 Hz), 4.40(d, 2H, J=5.3 Hz), 4.80 (t, 1H, J=5.3 Hz), 4.95-5.00 (m, 3H), 5.70 (t,1H, J=7.4 Hz), 6.69-6.73 (m, 1H), 6.94-6.95 (m, 1H), 7.09-7.20 (m, 4H),7.33 (s, 1H).

EXAMPLE 106(E)-3-Ethyl-7-[3-(3-hydroxymethylphenoxymethyl)phenyl]non-6-en-3-ol

In a manner identical to Examples 98 e, f, g, by reacting3-hydroxybenzaldehyde with[3-((E)-5-ethyl-1-methyl-5-triethylsilanyloxyhept-1-enyl)phenyl]methanol(obtained in Example 98 d), and then treating successively with lithiumaluminium hydride and then with tetrabutylammonium fluoride, acolourless oil is obtained.

¹H NMR (CDCl₃): 0.88 (t, 6H, J=7.5 Hz), 0.98 (t, 3H, J=7.3 Hz), 1.26 (s,1H), 1.48-1.60 (m, 6H), 2.17-2.27 (m, 2H), 2.53 (q, 2H, J=7.3 Hz), 4.62(s, 2H), 5.06 (s, 2H), 5.65 (t, 1H, J=7.2 Hz), 6.95-7.00 (m, 2H),7.26-7.31 (m, 5H), 7.39 (s, 1H).

EXAMPLE 107(E)-3-Ethyl-7-[3-(4-hydroxymethylphenoxymethyl)phenyl]non-6-en-3-ol

In a manner identical to Examples 98 e, f, g, by reacting4-hydroxybenzaldehyde with[3-((E)-5-ethyl-1-methyl-5-triethylsilanyloxyhept-1-enyl)phenyl]methanol(obtained in Example 98 d), and then treating successively with lithiumaluminium hydride and then with tetrabutylammonium fluoride, a whitepowder (m.p.=67-70° C.) is obtained.

¹H NMR (CDCl₃): 0.86 (t, 6H, J=7.5 Hz), 0.98 (t, 3H, J=7.3 Hz), 1.26 (s,1H), 1.47-1.60 (m, 6H), 2.17-2.27 (m, 2H), 2.53 (q, 2H, J=7.3 Hz), 4.66(s, 2H), 5.06 (s, 2H), 5.65 (t, 1H, J=7.2 Hz), 6.89-7.03 (m, 2H),7.24-7.30 (m, 5H), 7.40 (s, 1H).

EXAMPLE 108 Examples of Formulation

1) Oral Route

(a) The following composition is prepared in the form of a 0.2-g tablet

Compound of Example 1 0.005 g Pregelatinized starch 0.065 gMicrocrystalline cellulose 0.075 g Lactose 0.050 g Magnesium stearate0.005 g

For the treatment of ichthyosis, 1 to 3 tablets are administered to anadult individual per day for 1 to 12 months depending on the seriousnessof the case treated.

(b) An oral suspension intended to be packaged in 5-ml vials is prepared

Compound of Example 2 0.050 mg Glycerin 0.500 g Sorbitol at 70% 0.500 gSodium saccharinate 0.010 g Methyl para-hydroxybenzoate 0.040 gFlavouring qs 5 ml Purified water qs

For the treatment of acne, 1 vial is administered to an adult individualper day for 1 to 12 months depending on the seriousness of the casetreated.

(c) The following formulation intended to be packaged in gelatincapsules is prepared:

Compound of Example 4 0.0001 mg Maize starch 0.060 g Lactose qs 0.300 g

In the treatment of psoriasis, 1 gelatin capsule administered to anadult individual per day for 1 to months.

(d) The following formulation intended to be packaged in gelatincapsules is prepared:

Compound of Example 5 0.02 mg Cyclosporin 0.050 g Maize starch 0.060 gLactose qs 0.300 g

The gelatin capsules used consist of gelatin, titanium oxide and apreservative.

In the treatment of psoriasis, 1 gelatin capsule is administered to anadult individual per day for 1 to 12 months.

2) Topical Route

(a) The following nonionic Water-in-Oil cream is prepared:

Compound of Example 9 0.100 g Mixture of emulsive lanolin alcohols,39.900 g of waxes and of refined oils, sold by the company BDF under thename “Eucérine anhydre” Methyl para-hydroxybenzoate 0.075 g Propylpara-hydroxybenzoate 0.075 g Sterile demineralized water qs 100.000 g

This cream is applied to a psoriatic skin once or twice per day for 1 to12 months.

(b) A gel is prepared by producing the following formulation:

Compound of Example 18 0.001 g Erythromycin base 4.000 g Butylatedhydroxytoluene 0.050 g Hydroxypropylcellulose sold by the 2.000 gcompany Hercules under the name “KLUCEL HF” Ethanol (at 95%) qs 100.000g

This gel is applied to a skin affected by dermatosis or a skin with acne1 to 3 times per day for 6 to 12 weeks depending on the seriousness ofthe case treated.

(c) An antiseborrhoeic lotion is prepared by mixing the followingingredients:

Compound of Example 12 0.030 g Propylene glycol 5.000 g Butylatedhydroxytoluene 0.100 g Ethanol (at 95%) qs 100.000 g

This lotion is applied twice per day to a seborrhoeic scalp and asignificant improvement is served within a period of between 2 and 6weeks.

(d) A cosmetic composition against the harmful effects of the sun isprepared by mixing the following ingredients:

Compound of Example 27 1.000 g Benzylidene camphor 4.000 g Fatty acidtriglycerides 31.000 g Glycerol monostearate 6.000 g Stearic acid 2.000g Cetyl alcohol 1.200 g Lanolin 4.000 g Preservatives 0.300 g Propyleneglycol 2.000 g Triethanolamine 0.500 g Perfume 0.400 g Demineralizedwater qs 100.000 g

This composition is applied daily; it makes it possible to combatphotoinduced ageing.

(e) The following nonionic Oil-in-Water cream is prepared:

Compound of Example 38 0.500 g Retinoic acid 0.020 g Cetyl alcohol 4.000g Glycerol monostearate 2.500 g PEG 50 stearate 2.500 g Shea butter9.200 g Propylene glycol 2.000 g Methyl para-hydroxybenzoate 0.075 gPropyl para-hydroxybenzoate 0.075 g Sterile demineralized water qs100.000 g

This cream is applied to a psoriatic skin once or twice per day for 30days for intensive treatment and indefinitely for maintenance.

(f) A topical gel is prepared by mixing the following ingredients:

Compound of Example 49 0.050 g Ethanol 43.000 g α-Tocopherol 0.050 gCarboxyvinyl polymer sold under the 0.500 g name “Carbopol 941” by thecompany “Goodrich” Triethanolamine in aqueous solution 3.800 g at 20% byweight Water 9.300 g Propylene glycol qs 100.000 g

This gel is applied in the treatment of acne 1 to 3 times per day for 6to 12 weeks depending on the seriousness of the case treated.

(g) A hair lotion against hair loss and for regrowth is prepared bymixing the following ingredients:

Compound of Example 33 0.05 g Compound sold under the name 1.00 g“Minoxidil” Propylene glycol 20.00 g Ethanol 34.92 g Polyethylene glycol(molecular 40.00 g mass = 400) Butylated hydroxyanisole 0.01 g Butylatedhydroxytoluene 0.02 g Water qs 100.00 g

This lotion is applied once or twice per day for 3 months to a scalphaving suffered a loss of hair and indefinitely for maintenancetreatment.

(h) An antiacne cream is prepared by mixing the following ingredients:

Compound of Example 51 0.050 g Retinoic acid 0.010 g Mixture of glycerolstearates and 15.000 g polyethylene glycol (75 mol) sold under the name“Gelot 64” by the company “GATTEFOSSE” Polyoxyethylenated stone oil8.000 g containing 6 mol of ethylene oxide sold under the name “LabrafilM2130 CS” by the company “GATTEFOSSE” Perhydrosqualene 10.000 gPreservatives qs Polyethylene glycol (molecular 8.000 g mass = 400)Disodium salt of ethylenediamine- 0.050 g tetraacetic acid Purifiedwater qs 100.000 g

This cream is applied to a skin affected by dermatosis or a skin withacne 1 to 3 times per day for 6 to 12 weeks.

(i) An oil-in-water cream is prepared by producing the followingformulation:

Compound of Example 44 0.020 g Betamethasone 17-valerate 0.050 gS-carboxymethylcysteine 3.000 g Polyoxyethylenated stearate (40 mol4.000 g of ethylene oxide) sold under the name “Myrj 52” by the company“ATLAS” Sorbitan monolaurate, polyoxyethylene 1.800 g containing 20 molof ethylene oxide sold under the name “Tween 20” by the company “ATLAS”Mixture of glycerol mono- and 4.200 g distearate sold under the name“Géléol” by the company “GATTEFOSSE” Propylene glycol 10.000 g Butylatedhydroxyanisole 0.010 g Butylated hydroxytoluene 0.020 g Cetylstearylalcohol 6.200 g Preservatives qs Perhydrosqualene 18.000 g Mixture ofcaprylic-capric 4.000 g triglycerides sold under the name “Miglyol 812”by the company “DYNAMIT NOBEL” Triethanolamine (99% by weight) 2.500 gWater qs 100.000 g

This cream is applied twice per day to a skin affected by inflammatorydermatosis for 30 days.

(j) The following cream of oil-in-water type is prepared:

Lactic acid 5.000 g Compound of Example 8 0.020 g Polyoxyethylenatedstearate (40 mol 4.000 g of ethylene oxide) sold under the name “Myrj52” by the company “ATLAS” Sorbitan monolaurate, polyoxyethylene 1.800 gcontaining 20 mol of ethylene oxide sold under the name “Tween 20” bythe company “ATLAS” Mixture of glycerol mono- and 4.200 g distearatesold under the name “Géléol” by the company “GATTEFOSSE” Propyleneglycol 10.000 g Butylated hydroxyanisole 0.010 g Butylatedhydroxytoluene 0.020 g Cetylstearyl alcohol 6.200 g Preservatives qsPerhydrosqualene 18.000 g Mixture of caprylic-capric 4.000 gtriglycerides sold under the name “Miglyol 812”by the company “DYNAMITNOBEL” Water qs 100.000 g

This cream is applied once per day; it helps to combat ageing whetherphotoinduced or chronologic.

(k) The following anhydrous salve is prepared:

Compound of Example 19 5.000 g Liquid paraffin 50.00 g Butylatedhydroxytoluene 0.050 g Petroleum jelly qs 100 g

This salve is applied twice per day to a skin affected by squamosedermatosis for 30 days.

3) Intralesion Route

(a) The following composition is prepared:

Compound of Example 6 0.002 g Ethyl oleate qs 10 g

In the treatment of malignant melanoma, the composition is injected intoan adult individual at a frequency of 1 to 7 times per week for 1 to 12months.

(b) The following composition is prepared:

Compound of Example 11 0.050 g Olive Oil qs 2 g

In the treatment of basocellular carcinoma, the composition is injectedinto an adult individual at a frequency of 1 to 7 times per week for 1to 12 months.

(c) The following composition is prepared:

Compound of Example 36 0.1 mg Sesame oil qs 2 g

In the treatment of spinocellular carcinoma, the composition is injectedinto an adult individual at a frequency of 1 to 7 times per week for 1to 12 months.

(d) The following ocmposition is prepared:

Compound of Example 24 0.001 mg Methyl benzoate qs 10 g

In the treatment of colon carcinoma, the composition is injected into anadult individual at a frequency of 1 to 7 times per week for 1 to 12months.

4) Intravenous Route

(a) The following injectable lipid emulsion is prepared:

Compound of Example 47 0.001 mg Soya bean oil 10.000 g Egg phospholipid1.200 g Glycerin 2.500 g Water for injection qs 100.000 g

In the treatment of psoriasis, the composition is injected into an adultindividual at a frequency of 1 to 7 times per week for 1 to 12 months.

(b) The following injectable lipid emulsion is prepared:

Compound of Example 13 0.010 g Cottonseed oil 10.000 g Soya beanlecithin 0.750 g Sorbitol 5.000 g (DL)-α-Tocopherol 0.100 g Water forinjection qs 100.000 g

In the treatment of ichthyosis, the composition is injected into anadult individual at a frequency of 1 to 7 times per week for 1 to 12months.

(c) The following injectable lipid emulsion is prepared:

Compound of Example 29 0.001 g Soya bean oil 15.000 g Acetylatedmonoglycerides 10.000 g Pluronic F-108 1.000 g Glycerol 2.500 g Waterfor injection qs 100.000 g

In the treatment of leukaemia, the composition is injected into an adultindividual at a frequency of 1 to 7 times per week for 1 to 12 months.

(d) The following mixed micell composition is prepared:

Compound of Example 22 0.001 g Lecithin 16.930 g Glycocholic acid 8.850g Water for injection qs 100.000 g

In the treatment of malignant melanoma, the composition is injected intoan adult individual at a frequency of 1 to 7 times per week for 1 to 12months.

(e) The following cyclodextrin composition is prepared:

Compound of Example 31 0.1 mg β-Cyclodextrin 0.100 g Water for injectiongs 10.000 g

In the treatment of graft rejection, the composition is injected into anadult individual at a frequency of 1 to 7 times per week for 1 to 12months.

(f) The following cyclodextrin composition is prepared:

Compound of Example 4 0.010 g 2-Hydroxypropyl-β-cyclodextrin 0.100 gWater for injection qs 10.000 g

In the treatment of kidney cancer, the composition is injected into anadult individual at a frequency of 1 to 7 times per week for 1 to 12months.

EXAMPLE 109 Example of Test for Evaluating the Biological Activity ofthe Compounds of the Invention

The agonist activity for the vitamin D receptors of the compounds of theinvention may also be evaluated “in vivo” by the induction of24-Hydroxylase in SKH mice (Voorhees et al. 1997,108:513-518).

The test protocol used is the following:

SKH mice receive a single topical application of a compound according tothe invention in solution in ethanol in increasing concentrations. Avolume of 50 μl of the product to be tested or of the vehicle alone isapplied to the back of the mice with the aid of a pipette.

Other SKH mice receive a single topical application of1,25-(OH)₂-vitamin D₃ in solution in ethanol in increasingconcentrations. A volume of 50 μl of the product to be tested or of thevehicle alone is applied to the back of the mice with the aid of apipette.

8 hours after the topical application, the mice are humanely killed, theskin treated is removed and the epidermis is separated from the dermis.The quantification of the mRNA for 24-Hydroxylase is carried out bysemiquantitative PCR. The results are normalized with respect to theexpression of the mRNA for GAPDH and the values for the differentconcentrations of 1,25-(OH)₂-vitamin D₃ tested and for the differentcompounds of the invention tested are expressed as induction factorrelative to the vehicle.

The results are summarized in the following table:

Expression of the mRNA for 24-Hydroxylase

Concentration Induction factor Compound tested % (weight/volume) versusethanol 1,25-(OH)₂-vitamin D₃ 0.0001 6.7 1,25-(OH)₂-vitamin D₃ 0.00110.3 1,25-(OH)₂-vitamin D₃ 0.01 20.1 1,25-(OH)₂-vitamin D₃ 0.1 26Example 4  1 11 Example 59 0.1 20.5 Example 61 1 10 Example 65 1 15Example 68 0.1 25 Example 72 0.1 17 Example 82 0.1 21

These results show that the 1,25-(OH)₂-vitamin D₃ administered as asingle topical application induces in the mice, in a dose-dependentmanner, the expression of the mRNA for 24-Hydroxylase in the epidermis.

The biological activity of the compounds of the invention is evaluatedby comparison between the induction factors obtained for the compoundsof the invention and the induction factors obtained for1,25-(OH)₂-vitamin D₃.

Thus, the compound6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-ethylhepta-3,5-dien-2-ol(Example 4) exhibits, at the concentration of 1%, an activity comparableto that of 1,25-(OH)₂-vitamin D₃ at 0.001%.

What is claimed is:
 1. A compound having the formula (I):

wherein: R₁ represents a methyl radical or a radical —(CH₂)_(n)—OR₇; R₂represents a radical —(CH₂)_(n)—OR₈; X—Y represents a bond selected fromthe group consisting of the bonds of the following formulae (a) and (b)which are read from the left to the right or conversely:

R₃ represents the chain in vitamin D₂ or in vitamin D₃,

wherein the dotted lines represent the bond linking the R₃ chain to thebenzene ring represented in formula (I); or R₃ represents a chain havingfrom 4 to 8 carbon atoms which is substituted with one or more hydroxylgroups, the hydroxyl groups being optionally protected in the form ofacetoxy, methoxy, ethoxy, trimethylsilyloxy, tert-butyldimethylsilyloxy,or tetrahydropyranyloxy and the chain optionally in addition has atleast one feature selected from the following group: which issubstituted with one or more lower alkyl groups or cycloalkyl groups;which is substituted with one or more halogen atoms; which issubstituted with one or more CF₃ groups; wherein one or more carbonatoms of the chain are replaced by one or more oxygen, sulfur ornitrogen atoms, the nitrogen atoms being optionally substituted withlower alkyl radicals; and wherein one or more single bonds of the chainare replaced by one or more double and/or triple bonds; R₃ beingpositioned on the benzene ring at the para or meta position with respectto the X—Y bond; R₄, R₅ and R₆, which are identical or different,represent a hydrogen atom, a lower alkyl radical, a halogen atom, aradical —OR₁₀, or a polyether radical; n is 0, 1 or 2; R₇ and R₈, whichare identical or different, represent a hydrogen atom, an acetylradical, a trimethylsilyl radical, a tert-butyldimethylsilyl radical, ora tetrahydropyranyl radical; R₉ represents a hydrogen atom or a loweralkyl radical; W represents an oxygen atom, a sulfur atom, a radical—CH₂— or a radical —NH— which is optionally substituted with a loweralkyl radical; and R₁₀ represents a hydrogen atom or a lower alkylradical; or an optical or geometric isomer of the compound of formula(I) or a salt thereof.
 2. A compound having the formula (I):

wherein: R₁ represents a radical —(CH₂)_(n)—OR₇; R₂ represents a radical—(CH₂)_(n)—OR₈; X—Y represents a bond selected from the group consistingof the bonds of the following formulae (a) and (b) which are read fromthe left to the right or conversely:

R₃ represents the chain in vitamin D₂ or in vitamin D₃,

wherein the dotted lines represent the bond linking the R₃ chain to thebenzene ring represented in formula (I); or R₃ represents a chain havingfrom 4 to 8 carbon atoms which is substituted with one or more hydroxylgroups, the hydroxyl groups being optionally protected in the form ofacetoxy, methoxy, ethoxy, trimethylsilyloxy, tert-butyldimethylsilyloxy,or tetrahydropyranyloxy and the chain optionally in addition has atleast one feature selected from the following group: which issubstituted with one or more lower alkyl groups or cycloalkyl groups;which is substituted with one or more halogen atoms; which issubstituted with one or more CF₃ groups; wherein one or more carbonatoms of the chain are replaced by one or more oxygen, sulfur ornitrogen atoms, the nitrogen atoms being optionally substituted withlower alkyl radicals; and wherein one or more single bonds of the chainare replaced by one or more double and/or triple bonds; R₃ beingpositioned on the benzene ring at the para or meta position with respectto the X—Y bond; R₄, R₅ and R₆, which are identical or different,represent a hydrogen atom, a lower alkyl radical, a halogen atom, aradical —OR₁₀, or a polyether radical; n is 0, 1 or 2; R₇ and R₈, whichare identical or different, represent a hydrogen atom, an acetylradical, a trimethylsilyl radical, a tert-butyldimethylsilyl radical, ora tetrahydropyranyl radical; R₉ represents a hydrogen atom or a loweralkyl radical; W represents an oxygen atom, a sulfur atom, a radical—CH₂— or a radical —NH— which is optionally substituted with a loweralkyl radical; and R₁₀ represents a hydrogen atom or a lower alkylradical; or an optical or geometric isomer of the compound of formula(I) or a salt thereof.
 3. A compound according to claim 2, wherein thelower alkyl radicals are selected from the group consisting of methyl,ethyl, isopropyl, tert-butyl and hexyl radicals.
 4. A compound accordingto claim 2, wherein the cycloalkyl radical is an adamantyl radical or a1-methylcyclohexyl radical.
 5. A compound according to claim 2, whereinthe halogen atom is a fluorine, chlorine or bromine atom.
 6. A compoundaccording to claim 3, wherein the halogen atom is a fluorine, chlorineor bromine atom.
 7. A compound according to claim 4, wherein the halogenatom is a fluorine, chlorine or bromine atom.
 8. A compound according toclaim 2, wherein the polyether radical is a methoxymethoxy,methoxyethoxy or methoxyethoxymethoxy radical.
 9. A compound accordingto claim 2, having at least one characteristic selected from the groupconsisting of: (i) R₁ represents the radical —(CH₂)_(n)OH; (ii) R₂represents the radical —(CH₂)_(n)OH; (iii) X—Y represents a bond offormula (a); and (iv) R₃ represents a chain of 4 to 8 carbon atoms whichis substituted by at least one member selected from the group consistingof a hydroxyl radical and a lower alkyl radical.
 10. A compoundaccording to claim 2, wherein R₁ represents the radical —(CH₂)_(n)OH.11. A compound according to claim 2, wherein R₂ represents the radical—(CH)_(n)OH.
 12. A compound according to claim 2, wherein X—Y representsa bond of formula (a).
 13. A compound according to claim 2, wherein R₃represents a chain of 4 to 8 carbon atoms which is substituted by atleast one member selected from the group consisting of a hydroxylradical and a lower alkyl radical.
 14. A compound according to claim 2,wherein R₁ represents the radical —(CH₂)_(n)OH, R₂ represents theradical —(CH₂)_(n)OH, X—Y represents a bond of formula (a), and R₃represents a chain of 4 to 8 carbon atoms which is substituted by atleast one member selected from the group consisting of a hydroxylradical and a lower alkyl radical.
 15. The compound according to claim1, which is:3-hydroxymethyl-5-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;3-hydroxymethyl-5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol;3-[3-(5-hydroxy-1,5-dimethylhexyl)phenoxymethyl]-5-hydroxymethylphenol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhexan-2-ol;6-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-2-methylheptan-2-ol;7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloctan-3-ol;5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]ethyl}benzene-1,3-diol;5-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benene-1,3-diol;5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benene-1,3-diol;5-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]ethyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]ethyl}benzene-1,3-diol;2-hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylheptyl)phenyl]ethyl}phenol;2-hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]ethyl}phenol;2-hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol;2-hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol;2-hydroxymethyl-5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylheptan-2-ol;4-[3-(5-hydroxy-1,5-dimethylhexyl)phenoxymethyl]-2-hydroxymethylphenol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;7-{4-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;6-{4-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]-1-methylvinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol;5-[3-(6-hydroxy-6-methylheptyl)phenoxymethyl]benzene-1,3-diol;5-{2-[3-(7-hydroxy-7-methyloct-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(7-hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol;4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,2-diol;6-{3-[2-(3,5-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;7-{3-[2-(3,5-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;7-{3-[2-(4-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;7-[3-(3,4-bis-hydroxymethylphenylethynyl)phenyl]-2-methylheptan-2-ol;5-{2-[3-(6-hydroxy-6-methylhept-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(7-ethyl-7-hydroxynon-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(7-hydroxy-1-methoxy-1,7-dimethyloctyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-1-methoxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxypentyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxy-6-methylhept-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-7-methyloct-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(1,6-dihydroxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-1,6-dimethylhept-1-enyl)phenyl]vinyl}benzene-1,3-diol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-2-methylhexan-2-ol;5-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-2-methylpentan-2-ol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-3-ethylhexan-3-ol;7-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-3-ethylheptan-3-ol;5-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]ethylamino}-2-methylpentan-2-ol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]benzylamino}-3-ethylhexan-3-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylocta-4,6-dien-3-ol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-2-methylhepta-3,5-dien-2-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-3-ethylocta-4,6-dien-3-ol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2methylhepta-3,5-dien-2-ol;7-[3-(3,4-bis-hydroxymethylphenylethynyl)phenyl]-3-ethylocta-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;7-[4-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhept-3-en-2-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-4-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol;(E)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol;(Z)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol;(E)-9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol;(Z)-9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol;8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyl-2-nonanol;9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldecan-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-4-yn-3-ol;(3E,5E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2,7-dimethylocta-3,5-dien-2-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylocta-4,6-dien-3-ol;(3E,5E)-6-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-2-methylhepta-3,5-dien-2-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-6-en-3-ol;(Z)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-2-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-6-en-3-ol;(Z)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-5-en-2-ol;(Z)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol;(E)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol;8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnonan-3-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methylphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-5-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-4-methylphenyl]-3-ethylnona-4,6-dien-3-ol;1-[3-(3,4)-bis-hydroxymethylbenzyloxy)phenyl]ethanoneO-(2-hydroxy-2-methylpropyl)oxime;1{1-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]propoxy}-3-ethylpentan-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylnon-6-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzylsulfanyl)phenyl]-3-ethyloct-6-en-3-ol;(E)-7-{3-[(3,4-bis-hydroxymethylbenzyl)methylamino]phenyl}-3-ethyloct-6-en-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-6-methylhept-4-en-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctan-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3,7-diethylnonan-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1,1,1-trifluoro-2-trifluoromethyloct-5-en-2-ol;2-{4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]hexyl}-1,1,1,3,3,3-hexafluoropropan-2-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoronon-6-en-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyloctan-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-3-ol;(E)-4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1-cyclopropylhex-3-en-1-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnon-6-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methyldec-6-en-3-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylnona-4,6-dien-3-ol;(4E,6E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylnona-4,6-ol;(E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylnon-6-en-3-ol;(E)-3-ethyl-7-[3-(3-hydroxymethylphenoxymethyl)phenyl]non-6-en-3-ol;(E)-3-ethyl-7-[3-(4-hydroxymethylphenoxymethyl)phenyl]-non-6-en-3-ol;(E)-3-ethyl-7-[(E)-3-(3-hydroxymethyl-4-methylphenoxymethyl)phenyl]non-6-en-3-ol;(E)-3-ethyl-7-[(E)-3-(4-hydroxymethyl-3-methylphenoxymethyl)phenyl]non-6-en-3-ol;2-{4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-4-methylpentyl}-1,1,1,3,3,3-hexafluoropropan-2-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyloctan-3-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonan-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctane-3,4-diol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonane-3,4-diol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-7-methyloctane-3,4-diol;(E)-4-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-1-cyclopropylhex-3-en-1-ol;(4E,6E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-4-methylnona-4,6-dien-3-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnona-4,6-dien-3-ol;(E)-3-ethyl-7-[3-(4-hydroxymethyl-3-methylphenoxymethyl)phenyl]non-6-en-3-ol;(E)-3-ethyl-7-[3-(3-hydroxymethyl-4-methylphenoxymethyl)phenyl]non-6-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloct-6-en-3-ol;(E)-3-ethyl-7-[3-(3-hydroxymethylphenoxymethyl)phenyl]-non-6-en-3-ol; or(E)-3-ethyl-7-[3-(4-hydroxymethylphenoxymethyl)phenyl]-non-6-en-3-ol.16. A pharmaceutical composition comprising a therapeutically effectivevitamin D receptor agonist amount of at least one compound of formula(I) as claimed in claim 2 and a pharmaceutically acceptable carriertherefor.
 17. A composition according to claim 16, in oral dosage form.18. A composition according to claim 16, in topical dosage form.
 19. Acomposition according to claim 16, in injectable dosage form.
 20. Acomposition according to claim 16, wherein the concentration of compoundof formula (I) is between 0.001% and 5% by weight relative to the totalweight of the composition.
 21. A cosmetic composition comprising acosmetically effective vitamin D receptor agonist amount of at least onecompound of formula (I) as claimed in claim 2 and a cosmeticallyacceptable carrier therefor.
 22. A composition according to claim 21,wherein the concentration of compound of formula (I) is between 0.001%and 3% by weight relative to the total weight of the composition. 23.The compound which is:6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(3E,5E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2,7-dimethylocta-3,5-dien-2-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methylphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-5-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-4-methylphenyl]-3-ethylnona-4,6-dien-3-ol;or(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnona-4,6-dien-3-ol.24. The compound according to claim 22, which is:(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;or(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol.25. The compound according to claim 2, which is:3-hydroxymethyl-5-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;3-hydroxymethyl-5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol;3-[3-(5-hydroxy-1,5-dimethylhexyl)phenoxymethyl]-5-hydroxymethylphenol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhexan-2-ol;6-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-2-methylheptan-2-ol;7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloctan-3-ol;5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]ethyl}benzene-1,3-diol;5-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benene-1,3-diol;5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benene-1,3-diol;5-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]ethyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]ethyl}benzene-1,3-diol;2-hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]vinyl}phenol;2-hydroxymethyl-4-{2-[3-(5-hydroxy-5-methylheptyl)phenyl]ethyl}phenol;2-hydroxymethyl-4-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]ethyl}phenol;2-hydroxymethyl-4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol;2-hydroxymethyl-4-{2-[4-(6-hydroxy-6-methylheptyl)phenyl]ethyl}phenol;2-hydroxymethyl-5-{2-[4-(5-hydroxy-5-methylhexyl)phenyl]vinyl}phenol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylheptan-2-ol;4-[3-(5-hydroxy-1,5-dimethylhexyl)phenoxymethyl]-2-hydroxymethylphenol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;7-{4-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;6-{4-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;5-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]-1-methylvinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxy-5-methylhexyl)phenyl]vinyl}benzene-1,3-diol;5-[3-(6-hydroxy-6-methylheptyl)phenoxymethyl]benzene-1,3-diol;5-{2-[3-(7-hydroxy-7-methyloct-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(7-hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol;4-{2-[3-(6-hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,2-diol;6-{3-[2-(3,5-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;7-{3-[2-(3,5-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;7-[3-(3,4-bis-hydroxymethylphenylethynyl)phenyl]-2-methylheptan-2-ol;5-{2-[3-(6-hydroxy-6-methylhept-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(7-ethyl-7-hydroxynon-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(7-hydroxy-1-methoxy-1,7-dimethyloctyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-1-methoxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxypentyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxy-6-methylheptyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-7-methyloctyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(5-hydroxy-6-methylhept-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-7-methyloct-1-enyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(1,6-dihydroxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol;5-{2-[3-(6-hydroxy-1,6-dimethylhept-1-enyl)phenyl]vinyl}benzene-1,3-diol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-2-methylhexan-2-ol;5-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-2-methylpentan-2-ol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-3-ethylhexan-3-ol;7-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-3-ethylheptan-3-ol;5-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]ethylamino}-2-methylpentan-2-ol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]benzylamino}-3-ethylhexan-3-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylocta-4,6-dien-3-ol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-2-methylhepta-3,5-dien-2-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-3-ethylocta-4,6-dien-3-ol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhepta-3,5-dien-2-ol;7-[3-(3,4-bis-hydroxymethylphenylethynyl)phenyl]-3-ethylocta-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;7-[4-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhept-3-en-2-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-4-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol;(E)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol;(Z)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol;(E)-9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol;(Z)-9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol;8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyl-2-nonanol;9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldecan-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-4-yn-3-ol;(3E,5E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2,7-dimethylocta-3,5-dien-2-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylocta-4,6-dien-3-ol;(3E,5E)-6-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-2-methylhepta-3,5-dien-2-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-6-en-3-ol;(Z)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-2-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-6-en-3-ol;(Z)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-5-en-2-ol;(Z)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol;(E)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol;8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnonan-3-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methylphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-5-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-4-methylphenyl]-3-ethylnona-4,6-dien-3-ol;1-[3-(3,4)-bis-hydroxymethylbenzyloxy)phenyl]ethanoneO-(2-hydroxy-2-methylpropyl)oxime;1{1-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]propoxy}-3-ethylpentan-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylnon-6-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzylsulfanyl)phenyl]-3-ethyloct-6-en-3-ol;(E)-7-{3-[(3,4-bis-hydroxymethylbenzyl)methylamino]phenyl}-3-ethyloct-6-en-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-6-methylhept-4-en-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctan-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3,7-diethylnonan-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1,1,1-trifluoro-2-trifluoromethyloct-5-en-2-ol;2-{4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]hexyl}-1,1,1,3,3,3-hexafluoropropan-2-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoronon-6-en-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyloctan-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-3-ol;(E)-4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1-cyclopropylhex-3-en-1-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnon-6-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methyldec-6-en-3-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylnona-4,6-dien-3-ol;(4E,6E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylnona-4,6-dien-3-ol;(E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylnon-6-en-3-ol;2-{4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-4-methylpentyl}-1,1,1,3,3,3-hexafluoropropan-2-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyloctan-3-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonan-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctane-3,4-diol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonane-3,4-diol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-7-methyloctane-3,4-diol;(E)-4-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-1-cyclopropylhex-3-en-1-ol;(4E,6E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-4-methylnona-4,6-dien-3-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnona-4,6-dien-3-ol;or(E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloct-6-en-3-ol.26. A compound having the formula:

wherein: X—Y represents a bond selected from the group consisting of thebonds of the following formulae (a) and (b) which are read from the leftto the right or conversely:

R₃ represents the chain in vitamin D₂ or in vitamin D₃,

wherein the dotted lines represent the bond linking the R₃ chain to thebenzene ring represented in formula (I); or R₃ represents a chain havingfrom 4 to 8 carbon atoms which is substituted with one or more hydroxylgroups, the hydroxyl groups being optionally protected in the form ofacetoxy, methoxy, ethoxy, trimethylsilyloxy, tert-butyldimethylsilyloxy,or tetrahydropyranyloxy and the chain optionally in addition has atleast one feature selected from the following group: which issubstituted with one or more lower alkyl groups or cycloalkyl groups;which is substituted with one or more halogen atoms; which issubstituted with one or more CF₃ groups; wherein one or more carbonatoms of the chain are replaced by one or more oxygen, sulfur ornitrogen atoms, the nitrogen atoms being optionally substituted withlower alkyl radicals; and wherein one or more single bonds of the chainare replaced by one or more double and/or triple bonds; R₃ beingpositioned on the benzene ring at the para or meta position with respectto the X—Y bond; R₄, R₅ and R₆, which are identical or different,represent a hydrogen atom, a lower alkyl radical, a halogen atom, aradical —OR₁₀, or a polyether radical; R₉ represents a hydrogen atom ora lower alkyl radical; W represents an oxygen atom, a sulfur atom, aradical —CH₂— or a radical —NH— which is optionally substituted with alower alkyl radical; and R₁₀ represents a hydrogen atom or a lower alkylradical; or an optical or geometric isomer of the compound of formula(I) or a salt thereof.
 27. A compound according to claim 26, wherein thelower alkyl radicals are selected from the group consisting of methyl,ethyl, isopropyl, tert-butyl and hexyl radicals.
 28. A compoundaccording to claim 26, wherein the cycloalkyl radical is an adamantylradical or a 1-methylcyclohexyl radical.
 29. A compound according toclaim 26, wherein the halogen atom is a fluorine, chlorine or bromineatom.
 30. A compound according to claim 26, wherein X—Y represents abond of formula (a).
 31. A compound according to claim 26, wherein R₃represents a chain of 4 to 8 carbon atoms which is substituted by atleast one member selected from the group consisting of a hydroxylradical and a lower alkyl radical.
 32. A compound according to claim 26,wherein X—Y represents a bond of formula (a), and R₃ represents a chainof 4 to 8 carbon atoms which is substituted by at least one memberselected from the group consisting of a hydroxyl radical and a loweralkyl radical.
 33. The compound according to claim 26, which is:6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhepta-3,5-dien-2-ol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhexan-2-ol;6-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-2-methylheptan-2-ol;7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloctan-3-ol;6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylheptan-2-ol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;7-{4-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;6-{4-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;6-{3-[2-(3,5-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhexan-2-ol;7-{3-[2-(3,5-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylheptan-2-ol;7-[3-(3,4-bis-hydroxymethylphenylethynyl)phenyl]-2-methylheptan-2-ol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-2-methylhexan-2-ol;5-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-2-methylpentan-2-ol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-3-ethylhexan-3-ol;7-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]methylamino}-3-ethylheptan-3-ol;5-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]ethylamino}-2-methylpentan-2-ol;6-{[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]benzylamino}-3-ethylhexan-3-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylocta-4,6-dien-3-ol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-2-methylhepta-3,5-dien-2-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-3-ethylocta-4,6-dien-3-ol;6-{3-[2-(3,4-bis-hydroxymethylphenyl)vinyl]phenyl}-2-methylhepta-3,5-dien-2-ol;7-[3-(3,4-bis-hydroxymethylphenylethynyl)phenyl]-3-ethylocta-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylocta-4,6-dien-3-ol;7-[4-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-3-octanol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(4E,6Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnona-4,6-dien-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylhept-3-en-2-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-4-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-3-ol;(E)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol;(Z)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-7-en-2-ol;(E)-9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol;(Z)-9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-8-en-3-ol;8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyl-2-nonanol;9-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldecan-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyloct-6-en-4-yn-3-ol;(3E,5E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2,7-dimethylocta-3,5-dien-2-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylocta-4,6-dien-3-ol;(3E,5E)-6-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-2-methylhepta-3,5-dien-2-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-6-en-3-ol;(Z)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-2-ol;(Z)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyldec-6-en-3-ol;(Z)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methylnon-5-en-2-ol;(Z)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol;(E)-8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnon-7-en-3-ol;8-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethylnonan-3-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[5-(3,4-bis-hydroxymethylbenzyloxy)-2-methylphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-5-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-2-methoxyphenyl]-3-ethylnona-4,6-dien-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)-4-methylphenyl]-3-ethylnona-4,6-dien-3-ol;1-[3-(3,4)-bis-hydroxymethylbenzyloxy)phenyl]ethanoneO-(2-hydroxy-2-methylpropyl)oxime;1{1-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]propoxy}-3-ethylpentan-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethylnon-6-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzylsulfanyl)phenyl]-3-ethyloct-6-en-3-ol;(E)-7-{3-[(3,4-bis-hydroxymethylbenzyl)methylamino]phenyl}-3-ethyloct-6-en-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-6-methylhept-4-en-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctan-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3,7-diethylnonan-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1,1,1-trifluoro-2-trifluoromethyloct-5-en-2-ol;2-{4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]hexyl}-1,1,1,3,3,3-hexafluoropropan-2-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoronon-6-en-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyloctan-3-ol;(E)-6-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-2-methyloct-5-en-3-ol;(E)-4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-1-cyclopropylhex-3-en-1-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnon-6-en-3-ol;(E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methyldec-6-en-3-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylphenokymethyl)phenyl]-3-ethylnona-4,6-dien-3-ol;(4E,6E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylnona-4,6-dien-3-ol;(E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethylnon-6-en-3-ol;2-{4-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-4-methylpentyl}-1,1,1,3,3,3-hexafluoropropan-2-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4,4-difluoro-7-methyloctan-3-ol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonan-3-ol;7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-7-methyloctane-3,4-diol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3,7-diethylnonane-3,4-diol;7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-7-methyloctane-3,4-diol;(E)-4-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-1-cyclopropylhex-3-en-1-ol;(4E,6E)-7-{3-[2-(3,4-bis-hydroxymethylphenyl)ethyl]phenyl}-3-ethyl-4-methylnona-4,6-dien-3-ol;(4E,6E)-7-[3-(3,4-bis-hydroxymethylbenzyloxy)phenyl]-3-ethyl-4-methylnona-4,6-dien-3-ol;or(E)-7-[3-(3,4-bis-hydroxymethylphenoxymethyl)phenyl]-3-ethyloct-6-en-3-ol.34. A pharmaceutical composition comprising a therapeutically effectivevitamin D receptor agonist amount of at least one compound as claimed inclaim 26, and a pharmaceutically acceptable carrier therefor.
 35. Acomposition according to claim 34, in oral dosage form.
 36. Acomposition according to claim 34, in topical dosage form.
 37. Acomposition according to claim 34, in injectable dosage form.
 38. Acomposition according to claim 34, wherein the concentration of compoundis between 0.001% and 5% by weight relative to the total weight of thecomposition.
 39. A cosmetic composition comprising a cosmeticallyeffective vitamin D receptor agonist amount of at least one compound asclaimed in claim 26, and a cosmetically acceptable carrier therefor. 40.A composition according to claim 39, wherein the concentration ofcompound is between 0.001% and 3% by weight relative to the total weightof the composition.
 41. A compound having the formula:

wherein: R₃ represents a chain having from 4 to 8 carbon atoms which issubstituted with one hydroxyl group and optionally in addition issubstituted with one or more lower alkyl groups; wherein two singlebonds of the chain are replaced by two double bonds; and wherein R₃ ispositioned on the benzene ring at the para or meta position with respectto the —CH₂—O— group; and R₄ is hydrogen, a lower alkyl radical, or aradical of the formula —O—(lower alkyl); or an optical or geometricisomer or salt thereof.
 42. A compound according to claim 41, whereinthe lower alkyl radicals are selected from the group consisting ofmethyl, ethyl, isopropyl, tert-butyl and hexyl radicals.
 43. A methodfor treating a dermatological condition linked to a keratinocyte orsebocyte differentiation or proliferation disorder in a human or otheranimal in need of such treatment, said method comprising administeringto said human or other animal a therapeutically effective vitamin Dreceptor agonist amount of at least one compound of formula (I) asclaimed in claim
 2. 44. A method according to claim 43, wherein thecondition is acne vulgaris, comedo-type acne, polymorphic acne, acnerosacea, nodulocystic acne, acne conglobata, senile acne, secondaryacne, acne medicamentosa or occupational acne.
 45. A method for treatinga keratinization disorder selected from the group consisting ofichthyosis, ichthyosiform states, Darier's disease, keratosis palmerisand plantaris, leukoplasia, leukoplasiform states, cutaneous lichen andbuccal mucosal lichen in a human or other animal in need of suchtreatment, said method comprising administering to said human or otheranimal a therapeutically effective vitamin D receptor agonist amount ofat least one compound of formula (I) as claimed in claim
 2. 46. A methodfor treating a dematological condition linked to a keratinizationdisorder with an inflammatory component, with an immunoallergiccomponent, or with inflammatory and immunoallergic components, in ahuman or other animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D receptor agonist amount of at least one compound of formula(I) as claimed in claim
 2. 47. A method according to claim 46, whereinthe condition is psoriasis.
 48. A method according to claim 46, whereinthe condition is cutaneous psoriasis, mucosal psoriasis, ungualpsoriasis, psoriatic rheumatism or cutaneous atopy.
 49. A methodaccording to claim 46, wherein the condition is eczema, respiratoryatopy or gingival hypertropy.
 50. A method for treating an inflammatorycondition which does not exhibit a keratinization disorder, in a humanor other animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D receptor agonist amount of at least one compound of formula(I) as claimed in claim
 2. 51. A method for treating a dermal orepidermal proliferation which is benign or malignant in a human or otheranimal in need of such treatment, said method comprising administeringto said human on other animal a therapeutically effective vitamin Dreceptor agonist amount of at least one compound of formula (I) asclaimed in claim
 2. 52. A method according to claim 51, wherein theproliferation is of viral origin.
 53. The method according to claim 51,wherein the proliferation is verruca vulgaris, verruca plana orepidermodysplasia verruciformis.
 54. A method according to claim 51,wherein the proliferation comprises oral or florid papillomatoses.
 55. Amethod according to claim 51, wherein the proliferation is induced byultraviolet radiation.
 56. A method according to claim 51, wherein theproliferation comprises baso- and spinocellular epithelioma.
 57. Amethod for treating a bullous dermatosis or collagen disease in a humanor other animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D receptor agonist amount of at least one compound of formula(I) as claimed in claim
 2. 58. A method for treating photoinduced orchronologic skin ageing, pigmentation, actinic keratosis or otherpathology associated with chronologic or actinic ageing in a human orother animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D receptor agonist amount of at least one compound of formula(I) as claimed in claim
 2. 59. A method for treating a cicatrizationdisorder or vibicis in a human or other animal in need of suchtreatment, said method comprising administering to said human or otheranimal a therapeutically effective vitamin D receptor agonist amount ofat least one compound of formula (I) as claimed in claim
 2. 60. A methodfor treating a disorder of the sebaceous function in a human or otheranimal in need of such treatment, said method comprising administeringto said human or other animal a therapeutically effective vitamin Dreceptor agonist amount of at least one compound of formula (I) asclaimed in claim
 2. 61. A method according to claim 60, wherein thedisorder is hyperseborrhoea of acne, simple seborrhoea or seborrhoeiceczema.
 62. A method for treating an opthalmological disordersusceptible to treatment with a vitamin D receptor agonist in a human orother animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D receptor agonist amount of at least one compound of formula(I) as claimed in claim
 2. 63. A method according to claim 62, whereinthe disorder is a corneopathy.
 64. A method for treating a cancerous orprecancerous state of a cancer exhibiting or capable of being induced byvitamin D receptors in a human or other animal in need of suchtreatment, said method comprising administering to said human or otheranimal a therapeutically effective vitamin D receptor agonist amount ofat least one compound of formula (I) as claimed in claim
 2. 65. A methodaccording to claim 64, wherein said cancerous or precancerous state isbreast cancer, leukemia, myelodysplasic syndrome or lymphoma, carcinomaof the cells of the malpighian epithelium, gastrointestinal cancer,melanoma or osteosarcoma.
 66. A method for treating an inflammatorycondition susceptible to treatment with a vitamin D receptor agonist ina human or other animal in need of such treatment, said methodcomprising administering to said human or other animal a therapeuticallyeffective vitamin D receptor agonist amount of at least one compound offormula (I) as claimed in claim
 2. 67. A method according to claim 66,wherein the inflammatory condition is arthritis.
 68. A method accordingto claim 66, wherein the inflammatory condition is rheumatoid arthritis.69. A method for treating a condition of viral origin which issusceptible to treatment with a vitamin D receptor agonist in a human orother animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D agonist amount of at least one compound of formula (I) asclaimed in claim
 2. 70. A method for treating alopecia in a human orother animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D agonist amount of at least one compound of formula (I) asclaimed in claim
 2. 71. A method according to claim 70, wherein thealopecia is due to chemotherapy or radiation.
 72. A method for treatinga dermatological or general condition with an immunological componentwhich is susceptible to treatment with a vitamin D receptor agonist in ahuman or other animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D agonist amount of at least one compound of formula (I) asclaimed in claim
 2. 73. A method for treating an immunological conditionwhich is susceptible to treatment with a vitamin D receptor agonist in ahuman or other animal in need of such treatment, said method comprisingadministering to said human or other animal a therapeutically effectivevitamin D agonist amount of at least one compound of formula (I) asclaimed in claim
 2. 74. A method according to claim 73, wherein theimmunological condition is an autoimmune disease.
 75. A method accordingto claim 73, wherein the immunological condition is type 1 diabetesmellitus, multiple sclerosis, lupus, a lupus-type condition, asthma orglomerulonephritis.
 76. A method according to claim 73, wherein thecondition is a selective dysfunction of the immune system.
 77. A methodfor treating a hormonal condition which is susceptible to treatment witha vitamin D receptor agonist in a human or other animal in need of suchtreatment, said method comprising administering to said human or otheranimal a therapeutically effective vitamin D agonist amount of at leastone compound of formula (I) as claimed in claim
 2. 78. A method fortreating a condition characterized by abnormal management ofintracellular calcium in a human or other animal in need of suchtreatment, said method comprising administering to said human or otheranimal a therapeutically effective vitamin D agonist amount of at leastone compound of formula (I) as claimed in claim
 2. 79. A method fortreating a vitamin D deficiency or other condition of the homeostasis ofthe minerals in the plasma and bones in a human or other animal in needof such treatment, said method comprising administering to said human orother animal a therapeutically effective vitamin D agonist amount of atleast one compound of formula (I) as claimed in claim
 2. 80. A methodaccording to claim 79, wherein said vitamin D deficiency or othercondition comprises rickets, osteoporosis, renal osteodystrophy orparathyroid function disorder.
 81. A method according to claim 80,wherein the condition is osteoporosis in a menopausal woman.
 82. Amethod for cosmetically treating the body or hair of a human or otheranimal in need of such treatment, said method comprising topicallyapplying to the body or hair of said human or other animal acosmetically effective amount of a composition as claimed in claim 21.